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Determinants of prolonged mechanical ventilation after coronary artery bypass grafting
Determinants of Prolonged Mechanical Ventilation After Coronary Artery Bypass Grafting Robert H. Habib, PhD, Anoar Zacharias, MD, and Milo Engoren, MD Departments of Cardiothoracic Surgery, and Anesthesiology, St. Vincent Medical Center, Toledo, Ohio
Background. Early extubation of cardiac surgical patients enhances ambulation, improves cardiopulmonary function, and can lead to savings in health care costs. Methods. We retrospectively examined the role of 48 variables in determining the period of ventilatory support in 507 patients having coronary artery bypass grafting. Results. Fifteen (<30/o) of 507 patients required ventilatory support in excess of 24 hours. A m o n g the remaining patients, extubation was achieved early (_<8 hours) (mean time, 5.65 - 1.31 hours) in 53% and late (>8 hours) (mean time, 13.7 + 3.4 hours) in 47%. Logistic and linear multivariate regression analyses implicated increased age, N e w York Heart Association functional class IV, intraoperative fluid retention, postoperative intraaortic
balloon pump requirement, and bank blood transfusions as predictors of late extubation. Also, the linear regression linked lower body weight and number of anastomoses (or grafts) to increased mechanical ventilatory support. Conclusions. Analysis of the fluid balance and cardiopulmonary bypass data suggests that earlier extubation may be achieved by actively reducing fluid retention (eg, by hemoconcentration) and time on bypass (eg, normothermia). Finally, intensive care unit stay and postoperative length of stay were significantly lower in the early versus late extubation groups without an increase in pulmonary complications.
~
duration of ventilatory s u p p o r t r e m a i n s highly variable a m o n g patients, a n d studies that systematically explore the causes of this variability are needed. The p r i m a r y goal of this study was to elucidate the patient characteristics a n d operative variables responsible for p r o l o n g e d postoperative respiratory insufficiency in patients u n d e r g o i n g coronary artery bypass grafting (CABG). W e also sought to establish a m o d e l capable of predicting the n e e d of increased postoperative ventilatory s u p p o r t in CABG patients. Arguably, such a m o d e l w o u l d help identify areas of current practice w h e r e modifications might facilitate i m p r o v e d postoperative p u l m o n a r y function.
10r decades, overnight mechanical ventilation was used as s t a n d a r d postoperative care after a cardiac surgical procedure. The rationale for intentionally prolonging ventilatory s u p p o r t was that it m i n i m i z e d episodes of respirato D, insufficiency, hypertension, and patient anxiety [1]. Also, mechanical ventilation decreases the myocardial oxygen d e m a n d s resulting from spontaneous b r e a t h i n g [1]. Recent practice has focused on expediting w e a n i n g from mechanical ventilation. The clinical a d v a n t a g e s of early extubation are mainly that it reduces the possibility of adverse effects of positivepressure ventilation (eg, b a r o t r a u m a ) and minimizes associated patient discomfort, potentially decreases the incidence of infection, and expedites early ambulation. The growing frequency of open heart operations and their high costs have also increased interest in early extubation as a means of reducing intensive care and hospitalization costs [2, 3]. Methods of w e a n i n g cardiac surgical patients from mechanical ventilation continue to evolve a n d can vary greatly a m o n g institutions. Advances in techniques of anesthesia a n d c a r d i o p u l m o n a r y b y p a s s as well as analgesic medications have b e e n i n s t r u m e n t a l in reducing postoperative ventilatory d e p e n d e n c y without increasing the incidence of p u l m o n a r y complications in patients who have u n d e r g o n e an open heart p r o c e d u r e [41. These advances, in turn, have led to appreciable declines in duration of intensive care a n d hospitalization. However,
(Ann Thorac Surg 1996;62:1164-71)
Material a n d M e t h o d s We retrospectively reviewed the case reports of a total of 522 patients who u n d e r w e n t CABG-only p r o c e d u r e s at our institution in 1994. There were six operative deaths (1.1%), and 9 patients (1.7%) had an exceedingly complicated postoperative course with p r o l o n g e d hospitalization (>33 days). These 9 patients were considered outliers as p e r Medicare guidelines a n d were excluded from further analysis. Hence, the study group c o m p r i s e d 507 patients. All patients were o p e r a t e d on a n d cared for by the s a m e group of surgeons, anesthesiologists, a n d cardiovascular intensive care staff.
Perfusion Accepted for publication May 19, 1996. Address reprint requests ~o Dr Zacharias, St. Vincent Medical Center, 2213 Cherry St, ACC 309, Toledo, OH 43608. © 1996 by The Society of Thoracic Surgeons Published bv Elsevier Science Inc
C a r d i o p u l m o n a r y bypass was c o n d u c t e d with an extracorporeal circuit consisting of a m e m b r a n e oxygenator (Baxter Healthcare Corp, Irvine, CA), a centrifugal p u m p 0003-49751961515.00 P[I S0003-4975(96)00565-6
Ann Thorac Surg 1996;62:1164-71
( M e d t r o n i c , Inc, A n a h e i m , CA), a n d t h e c a p a c i t y for u l t r a f i l t r a t i o n . Typically, t h e p u m p w a s p r i m e d w i t h 1,800 m L of P l a s m a l y t e , 50 g of m a n n i t o l (250 mL), a n d 50 g of a l b u m i n (200 mL). O n e s u r g e o n ( s u r g e o n A) d i d n o t u s e a l b u m i n (n = 106 p a t i e n t s ) . N o r m o t h e r m i c (lowest core t e m p e r a t u r e > 3 5 ° C ) p e r f u s i o n w a s u s e d i n t h e m a j o r i t y of p a t i e n t s (89%) w i t h t h e c i r c u i t ' s h e a t e r / c o o l e r t e m p e r a t u r e set at 38°C. M i l d ( l o w e s t core t e m p e r a t u r e = 32 ° to 35°C) h y p o t h e r m i a a n d m o d e r a t e (27°C < l o w e s t c o r e t e m p e r a t u r e < 32°C) h y p o t h e r m i a w e r e u s e d less f r e q u e n t l y (2% a n d 9%, r e s p e c t i v e l y ) . U l t r a f i l t r a t i o n w a s u s e d in a few p a t i e n t s d i a g n o s e d w i t h a n a s a r c a (5/507, 1%). C a r d i o p l e g i a w a s m o s t l y a n t e g r a d e a n d c o n s i s t e d of P l e g i s o l w i t h 1 g of l i d o c a i n e h y d r o c h l o r i d e , 50 m E q of KC1, a n d 15 g of N a H C O 3 (8.4%) in e i t h e r c o l d o x y g e n a t e d c r y s t a l l o i d s o l u t i o n or c o l d b l o o d . A r t e r i a l b l o o d flows w e r e d e t e r m i n e d o n t h e b a s i s of a c a r d i a c i n d e x of 2.5 to 3.0 (L • m i n ~ • m 2), a n d m e a n a r t e r i a l p r e s s u r e s w e r e m a i n t a i n e d b e t w e e n 50 a n d 60 m m Hg.
Anesthesia and Analgesia A n e s t h e s i a a n d a n a l g e s i a w e r e s t a n d a r d i z e d for all p a t i e n t s to m i n i m i z e r e s p i r a t o r y d r i v e a n d t h u s facilitate e a r l i e r e x t u b a t i o n . Briefly, p a t i e n t s w e r e p r e m e d i c a t e d m o s t l y w i t h l o r a z e p a m . A f t e r t h e e s t a b l i s h m e n t of a n a r t e r i a l l i n e a n d a p e r i p h e r a l v e n o u s line, a n e s t h e s i a w a s induced with fentanyl and diazepam. Sodium thiopental (0 to 250 m g ) w a s g i v e n to a c h i e v e a m e a n a r t e r i a l p r e s s u r e of 70 m m Hg. P a n c u r o n i u m b r o m i d e w a s u s e d for m u s c l e r e l a x a t i o n . A f t e r d i r e c t l a r y n g o s c o p y , 4 m L of l i d o c a i n e s o l u t i o n (4%) w a s a p p l i e d to t h e t r a c h e a a n d larynx, a n d t h e p a t i e n t w a s i n t u b a t e d . A n e s t h e s i a a n d muscle relaxation were maintained with isoflurane and s m a l l a d d i t i o n a l d o s e s of f e n t a n y l , d i a z e p a m , a n d p a n c u r o n i u m . T h e t o t a l a m o u n t s of d i a z e p a m a n d f e n t a n y l w e r e c o n t r o l l e d fairly r i g i d l y so as n o t to e x c e e d 10 m g / k g a n d 30 ~ g / k g , r e s p e c t i v e l y . Postoperative analgesia was achieved with ketorolac u n l e s s c o n t r a i n d i c a t e d ( A p p e n d i x 1). C o n t r a i n d i c a t i o n s w e r e a g e g r e a t e r t h a n 70 years, a s e r u m c r e a t i n i n e l e v e l h i g h e r t h a n 1.3 m g / d L , a n d a h i s t o r y of s e n s i t i v i t y to nonsteroid, antiinflammatory drugs. Morphine was used in p a t i e n t s w h e n k e t o r o l a c w a s n o t sufficient. D i a z e p a m a n d h a l o p e r i d o l w e r e u s e d for a n x i o l y s i s a n d a g i t a t i o n , r e s p e c t i v e l y . S m a l l d o s e s (12.5 to 25 m g ) of m e p e r i d i n e h y d r o c h l o r i d e w e r e a d m i n i s t e r e d to r e v e r s e s h i v e r i n g , a n d d o s e s of p a n c u r o n i u m or v e c u r o n i u m b r o m i d e (0.5 to 1 mg) were used when meperidine was inadequate.
Criteria for Extubation Once patients were hemodynamically stable and responsive to c o m m a n d s , v e n t i l a t o r w e a n i n g w a s s t a r t e d as d e s c r i b e d in A p p e n d i x 2 [5]. Briefly, p a t i e n t s w e r e e x t u b a t e d w h e n t h e y m e t s t a n d a r d m e c h a n i c a l f u n c t i o n crit e r i a a n d w e r e a b l e to m a i n t a i n n o r m a l b l o o d g a s e s o n c o n t i n u o u s p o s i t i v e - a i r w a y p r e s s u r e or a n i n t e r m i t t e n t m a n d a t o r y v e n t i l a t i o n r a t e of 4 b r e a t h s / r a i n w i t h a n i n s p i r e d o x y g e n f r a c t i o n of less t h a n or e q u a l to 40%. Standard criteria included an appropriate respiratory rate, t i d a l v o l u m e g r e a t e r t h a n 5 m L / k g , vital c a p a c i t y
HABIB ET AL EARLY EX~fUBATIONAFTER CORONARY BYPASS
1165
Table 1. Univariate Analysis of Patient Characteristics and Preoperative Data"
Variable Age (y) Weight (kg) BSA (m 2) Preop BUN Preop creatinine Preop hemoglobin Female sex (%) MI (%) Acute MI (%) Unstable angina ('",) Preop IABP (%) CHF (o,) Renal insufficiency (%) Preop diuretics (%) Smoker (%) COPD (%) Obese (%) Diabetes (",.) Insulin dependence (%) Hypercholesterolemia (%) LMD (%) Hypertension (%) Pulmonary hypertension (%) History, of CAD (%) Same-day admission (%) Emergency (%) Redo CABG (%) NYHA class IV (%)
Early Extubation (T,~t < 8 h) (n 259; 52.6%)
Late Extubation (8 h < T~× t -<24 h) (n = 233; 47.4%)
60.2 ÷ 10.0 88.5 + 16.6 2.01 + 0.21 14.8 ÷ 5.2 1.06 -+ 0.72 14.0 _+ 1.45 20.6 56.7 6.0 27.0 3.2 4.0 1.2 12.7 65.9 17.9 17.5 25.8 8.3 66.3 12.7 80.6 1.2
64.7 -+ 10.3 82.1 z 17.2 1.91 ± 0.22 16.1 ± 6.9 1.09 ± 0.68 13.7 ± 1.56 33.0 55.1 8.8 29.1 3.5 8.8 1.8 18.9 64.3 16.3 12.3 32.6 13.2 61.7 14.5 84.1 1.3
63.1 46.8 3.6 3.6 36
67.0 51.4 5.7 2.2 47
p Value b < < < < < < <
0.001 0.001 0.001 0.05 0.07 0.06 0.003 ... ... ... ... < 0.05 ... 0.08 ... ... 0.15 0.12 0.11 ... ... ... ...
... ... ... ... < 0.001
.~Where applicable, data are shown as the mean - the standard deviation. i, Only p values of less than 0.25 in the univariate analysis are reported to indicate variables used in the multivariate analysis. BSA = body surface area; BUN blood urea nitrogen; CABG coronary artery bypass grafting; CAD - coronary artery disease; CHF congestive heart failure; COPD ~ chronic obstructive pulmonarv disease; I A B P intraaortic balloon pump; LMD left main disease; MI - myocardial infarction (acute - less than 24 hours); NYHA New York Heart Association; Te~ t - time to extubation.
g r e a t e r t h a n 10 m L / k g , a n d n e g a t i v e i n s p i r a t o r y force g r e a t e r t h a n 20 m m Hg. T i m e to e x t u b a t i o n (Te×t) o r hours on mechanical ventilation were calculated from t i m e o u t of t h e o p e r a t i n g r o o m , r o u n d e d to t h e c l o s e s t half hour, and recorded.
Statistical Methods P a t i e n t s w e r e d i v i d e d i n t o e a r l y ( T ~ × t < 8 h o u r s ) a n d late (8 < T~×t < 24 h o u r s ) e x t u b a t i o n g r o u p s . T w e n t y - e i g h t p r e o p e r a t i v e ( T a b l e 1), 13 i n t r a o p e r a t i v e , a n d 7 p o s t o p e r a t i v e v a r i a b l e s ( T a b l e 2) w e r e c o m p a r e d . U n i v a r i a t e a n a l y s i s ( S i g m a S t a t ; J a n d e l Scientific, S a n R a p h a e l , C A ) w a s d o n e w i t h X2 or F i s h e r ' s e x a c t t e s t for c a t e g o r i c
1166
HABIBET AL EARLY EXTUBAT1ON AFTER CORONARY BYPASS
Ann Thorac Surg 1996;62:1164-71
v a r i a b l e s a n d e i t h e r t h e u n p a i r e d t test or t h e n o n p a r a m e t r i c M a n n - W h i t n e y r a n k s u m t e s t for c o n t i n u o u s v a r i ables, d e p e n d i n g o n a p p l i c a b i l i t y . Multivariate analysis was performed with backward e l i m i n a t i o n logistic r e g r e s s i o n s (SAS I n s t i t u t e Inc, C a r y , N C ) a n d s t e p w i s e l i n e a r r e g r e s s i o n s ( S i g m a S t a t ) . For u n i v a r i a t e s i g n i f i c a n c e levels, w e u s e d a p v a l u e of less t h a n 0.25 for c o v a r i a t e i n c l u s i o n a n d a p v a l u e of less t h a n 0.05 for c o v a r i a t e r e t e n t i o n . T h e logistic a n d l i n e a r m o d els p r o v i d e d t h e i n d e p e n d e n t p r e d i c t o r s of a binary.
Table 2. Univariate Analysis of Intraoperative and Postoperative Variables' ,b
Variable lntraoperative Blood removal (mL) No of anastomoses No. of proximal anastomoses No. of grafts/distal anastomoses Pump time (min) Cross-clamp time (rain) LCT (°C) Fluid balance (mL) Fluid balance/BSA (mL/m 2) Postop hemoglobin Surgeon (%) A
B C D Perfusion (%) Normothermia Mild hypothermia Moderate hypothermia Albumin (%) Postoperative Periop IABP (%) Periop MI (%) Bank blood transfusions (",,) Renal failure (%) Neurologic event (%) Postop bleeding (%) Arrhythmia (%) Atrial fibrillation Ventricular fibrillation
Earlv Extubation (T~,x, < 8 h)
Late Extubation (8 h <3 p T~.~t< 24 h) Value"
273 ~ 157 5.02 ~ 1.87 1.98 ± 0.90
244 ÷ 171 5.45 ~ 1.78 2.20 ? 0.87
0.17 < 0.02 <: 0.02
3.02 :~ 1.02
3.22 + 0.97
•: 0.04
88.2 51.8 35.3 1,179 585
~ ~ ~ -
30.8 95.3 + 19.8 54.3 + 1.9 34.8 ~ 1,010 1,448 + 500 762 +
7.42 - 1.61
34.9 <- 0.05 20.6 0.16 2.2 1,041 < 0.005 562 < 0.001
7.18 * 1.39
55 48 55 55
45 52 45 45
90.5 2.8 6.7 77
85.9 1.3 12.8 79
4.0 0.8 14.7
9.3 0.9 32.6
0 0 0.8
1.3 0.4 1.3
0.4 0
1.8 0.4
< 0.02 0.06
• 0.05
< 0.05 < 0.001
0.18
~ Postoperative data were obtained during stay in cardiovascular intensive care unit. b Where applicable, data are shown as the mean + the standard deviation. ~ Only p values of less than 0.25 in the univariate analysis are reported so as to indicate variables used in the multivariate analysis. BSA bodv surface area; LCT lowest core temperature; time to extubation.
IABP intraaortic balloon pump; MI mvocardial infarction; T~,t
(early v e r s u s late) a n d a c o n t i n u o u s (Tex t i n h o u r s ) r e p r e s e n t a t i o n of Text, r e s p e c t i v e l y . T h e t w o t y p e s of m u l t i v a r i a t e a n a l y s i s w e r e u s e d to d e t e r m i n e w h e t h e r a f o r c e d b i n a r y d e s c r i p t i o n of Tex t i n f l u e n c e d t h e r e s u l t s b y e x c l u d i n g i m p o r t a n t or r e t a i n i n g u n i m p o r t a n t i n d e p e n dent predictors or both.
Results F i g u r e 1 i l l u s t r a t e s t h e f r e q u e n c y d i s t r i b u t i o n of Te× t i n 507 C A B G p a t i e n t s . Briefly, 51% of p a t i e n t s w e r e e x t u b a t e d w i t h i n 8 h o u r s ( m e d i a n T~×t = 8 h o u r s ) , a n d less t h a n 3% of p a t i e n t s (15/507) r e q u i r e d v e n t i l a t o r y s u p p o r t for m o r e t h a n 24 h o u r s . In g e n e r a l , t h e p a t i e n t s w e r e d i v i d e d i n t o t w o g r o u p s o n t h e b a s i s of t h e n e a r l y b i m o d a l f r e q u e n c y d i s t r i b u t i o n of Te×t: (1) a n e a r l y e x t u b a t i o n g r o u p (T,,xt < 8 h o u r s , m e d i a n = 5.5 h o u r s , n 259) a n d (2) a late e x t u b a t i o n g r o u p (8 < Tex t G 24, m e d i a n - 13.5 h o u r s , n - 233). P r e o p e r a t i v e d a t a for t h e t w o g r o u p s a r e c o m p a r e d in T a b l e 1. H e r e , t h e r e t r o s p e c t i v e u n i v a r i a t e a n a l y s i s r e v e a l e d t h a t p a t i e n t s in t h e late e x t u b a t i o n g r o u p w e r e a n a v e r a g e of 4.5 y e a r s older, i n c l u d e d m o r e f e m a l e p a t i e n t s (33% v e r s u s 21%), a n d w e r e a n a v e r a g e of 6.4 k g s m a l l e r . Also, p a t i e n t s in t h i s g r o u p w e r e g e n e r a l l y s i c k e r t h a n t h o s e i n t h e e a r l y e x t u b a t i o n g r o u p , as t h e y h a d t w i c e t h e i n c i d e n c e of c o n g e s t i v e h e a r t f a i l u r e (8.8% v e r s u s 4.0%), a h i g h e r p e r c e n t a g e of t h e m w e r e in N e w Y o r k H e a r t A s s o c i a t i o n class IV, a n d t h e p r e o p e r a t i v e b l o o d u r e a nitrogen and creatinine levels were higher. The dec r e a s e d p r e o p e r a t i v e h e m o g l o b i n level, t h e i n c r e a s e d c r e a t i n i n e level, a n d t h e m o r e f r e q u e n t u s e of p r e o p e r a tive d i u r e t i c s in t h e late e x t u b a t i o n g r o u p all a p p r o a c h e d significance. lntraoperative and postoperative data are summarized in T a b l e 2. E l e v e n v a r i a b l e s ( n i n e i n t r a o p e r a t i v e a n d t w o postoperative) differed significantly between the early a n d late e x t u b a t i o n g r o u p s . P a t i e n t s in t h e late g r o u p g e n e r a l l y r e c e i v e d m o r e g r a f t s (3.22 v e r s u s 3.02), a n d total c a r d i o p u l m o n a r y b y p a s s t i m e w a s l o n g e r b y a n a v e r a g e of 7.1 m i n u t e s . A l t h o u g h e m p l o y e d i n o n l y a s m a l l n u m b e r of p a t i e n t s , u s e of m o d e r a t e h y p o t h e r m i a w a s n e a r l y t w i c e as f r e q u e n t for t h e late g r o u p (12.8% v e r s u s 6.7%). Also, a b s o l u t e fluid r e t e n t i o n (liters) calcul a t e d f r o m t h e t o t a l f l u i d i n p u t v e r s u s o u t p u t w a s 22% h i g h e r a f t e r b y p a s s i n t h e late e x t u b a t i o n g r o u p c o m pared with the early extubation group. This difference w a s i n c r e a s e d to 30% w h e n fluid b a l a n c e w a s n o r m a l i z e d to t h e p a t i e n t ' s b o d y s u r f a c e area. O n t h e o t h e r h a n d , h e m o g l o b i n c o n c e n t r a t i o n s w e r e g e n e r a l l y l o w e r for t h e late e x t u b a t i o n g r o u p t h a n t h e e a r l y e x t u b a t i o n g r o u p . P o s t o p e r a t i v e b a n k b l o o d t r a n s f u s i o n s (32.6% v e r s u s 14.7%) a n d u s e of i n t r a a o r t i c b a l l o o n p u m p s (9.3% v e r s u s 4.0%) w e r e m o r e f r e q u e n t in t h e late g r o u p . S e v e r a l of t h e 18 v a r i a b l e s l i n k e d to late e x t u b a t i o n b y u n i v a r i a t e a n a l y s i s are c o r r e l a t e d (eg, n u m b e r s of g r a f t s a n d p e r f u s i o n t i m e ) a n d h e n c e m a y n o t all b e i n d e p e n d e n t p r e d i c t o r s of p r o l o n g e d m e c h a n i c a l v e n t i l a t i o n . Acc o u n t i n g for c o d e p e n d e n c e of v a r i a b l e s , t h e m u l t i v a r i a t e logistic m o d e l i n c l u d e d a t o t a l of five i n d e p e n d e n t p r e -
Ann Thorac Surg 1996;62:1164-71
HABIB ET AL EARLY EXTUBATION AFTER C O R O N A R Y BYPASS
Fig 1. Bimodal frequency distribution of time on ventilatory support in 507 patients undergoing coron a r y artery bypass grafting. D o t t e d l i n e depicts the median time to extubation (T ,~t) of 8 hours, w h i c h also separates the bimodal patient population into early ( w h i t e b a r s ) and late ( b l a c k b a r s ) extubation groups.
100
Early
80
g
o~
1167
60
"6 c~
40
E Z
20
i.===..= i
i
i
i
i
8
12
16
20
24
Time to Extubation (Text, Hours)
dictors of late extubation (Table 3). These were older age, N e w York Heart Association class IV, increased positive fluid balance normalized to body surface area, use of postoperative intraaortic balloon pump, and bank blood transfusions. In addition to these five variables, the stepwise multivariate linear regression analysis also implicated smaller patient weight and increased number of anastomoses or grafts as predictors of increased Te× t (Table 4). Besides avoiding categorizing patients into groups (ie, late and early), the linear model also permitted a more straightforward interpretation of the relative impact of each of the predictors of Text. For instance, all else being equal, the linear model coefficient estimated for age (0.06) translates to an average increase of 0.6 hour in mechanical ventilation for every 10-year increase in patient age. S i m i l a r l y , Te× t is expected to increase by I hour for every 1 L/m 2 increase in fluid retention. On the other hand, postoperative intraaortic balloon pump use and blood transfusions (categoric variables), when indicated, inc r e a s e T~× t by 2.92 and 1.3 hours, respectively.
open heart operation, to early extubation is a delicate process involving a collaborative effort from surgeons, anesthesiologists, and intensive care staff. In our experience, implementation of early extubation has been a dynamic process that continues to evolve as the medical team providing patient care becomes more experienced. The main goals of this study were to identify the patient characteristics and operative variables that distinguish early extubation and late extubation patient groups, to build a model capable of predicting delayed extubation in CABG patients, and to identify and explore possible areas of surgical and medical practice where modifications may allow earlier extubation. Four of the seven factors implicated by the retrospective multivariate analysis have a direct impact on postoperative recovery. Of these, increased age, N e w York Heart Association class IV, and more frequent blood transfusions indicate a weaker or sicker patient, and increased postoperative use of the intraaortic balloon
Table 4. Independent Predictors of the Continuous Variable Time to Extubation by Stepwise Multivariate Linear Regression Analysis
Comment The change in practice from intentionally prolonged ventilation, advocated for decades for patients having an
Table 3. Independent Predictors of Early Versus Late Extubation by Multivariate Logistic Regression Analysis
Covariate
Odds Ratio
p Value
A g e (y)
1.035
1,02 to 1.06
< 0.0001
N Y H A IV ( Y / N )
1.634
1,10 to 2.43
0.02
Fluid balance/BSA ( m L / m 2)
1.001
1.000 to 1,001
<- 0.0001
Periop IABP (Y/N)
2.551
1.10 to 5.92
0.03
Bank blood transfusions (Y/N)
2.412
1.48 to 3.94
<- 0.0001
N
Standard Error
p Value
Constant (hi b
5.82
1.97
...
A g e (y)
0.06
0.02
0.005
W e i g h t (kg)
95% Confidence Interval
BSA = b o d y surface area; IABP = intraaortic balloon p u m p ; no; NYHA :: New York Heart Association; Y yes.
Coefficient" (al-a7)
Covariate
-0.03
0.01
0.01
N Y H A c l a s s IV ( Y / N )
1.00
0.42
0.02
No. of anastomoses
0.24
0.11
0.04
0.001
0.0004
0.01
Periop IABP (Y/N)
2.92
1.04
0.005
Bank blood transfusions
1.30
0.52
0.01
Fluid balance/BSA
( m L / m 2)
" Positive/negative coefficient values indicate increased time to extubation (in hours) with increased~decreased value of numerical variables or incidence/absence of categoric variables. 6 Constant is the additive quanti~" in the multiple linear regression model: Time to extubation = a~ x age + a 2 ?K weight 4- a 3 × NYHA class IV + a 4 x anastomoses + a5 × fluid balance normalized to BSA 4- a~, × periop IABP + a7 × b a n k blood transfusion ~ constant, BSA no;
b o d y surface area; IABP intraaortic balloon pump; NYHA - N e w York H e a r t Association; Y yes.
N -
1168
HABIB ET AL EARLY EXTUBATION
AFTER
CORONARY
Ann Thorac Surg 1996;62:1164-71
BYPASS
p u m p indicates persistent hemodvnamic instability and left ventricular dysfunction. Intraoperative fluid retention associated with cardiopulmonary bypass can lead to substantial lung dysfunction [6-8]. A major component of the positive fluid balance retained by the patient at the end of operation is in the form of increased extravascular lung water. Obviously, such pulmonary edema can impair pulmonary function by its deleterious effects on lung mechanics and gas exchange. Extravascular lung water can be further increased in the early postoperative hours after pulmonary reperfusion commences [6]. Movement of fluid between the intravascular and extravascular spaces of the lung can depend on both the degree of hemodilution, through its effects on oncotic pressures, and the endothelial integrity, of the pulmonary vasculature [6]. The linear regression analysis provided evidence in support of this notion (see Table 4). Here, analysis of the time on mechanical ventilation as a continuous variable implicated two additional factors: n u m b e r of anastomoses and patient weight. Time on cardiopulmonary bypass increases with the n u m b e r of grafts (or anastomoses) and has been shown to cause endothelial injury, which increases permeability of the pulmonary vasculature [6-8]. This p h e n o m e n o n has been linked to complement activation and release of inflammatory mediators subsequent to the exposure of blood (leukocytes) to the surface of the extracorporeal circuit during bypass [6-8]. We speculate that decreased patient body weight has an indirect impact on postoperative lung function through its role in fluid retention. To explain this contention, we suggest the following scenario: The oncotic
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100
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120
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140
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Fig 2. Tendcncy.ti}r increased postoperative hemoglobin concentration (inversely related to hemodilution) to be a hmction qfi increased patient body weight. Dots are individual patient data. Squares are averaged data over a range qf patient body weights. Lines represent linear regressions (solid line) (r 0.47), 95% confidence inte~,als (broken lines), and prediction inte~,al (dash-dot lines)•
Table 5. Independent Predictors of Fluid Balance Normalized to Body Surface Area
Covariate Constant (mL/m2)•' Age (y) BUN T..... {rain) Albumin (Y/N)
Coefficient (a i-a=) 186 5.83 10.2 1.81 253
Standard Error
p Value
168 2.44 4.08 0•80 63
... 0.02 0.01 0.02 < 0.0001
-' C o n s t a n t is t h e a d d i t i v e q u a n t i t ) in the multiple linear regression model: Fluid balance normalized t o B S A = a I x a g e + a z × B U N 4 a~ × "1~ Pt* + a4 ~ a l b u m i n + c o n s t a n t . BSA no; ves.
=, b o d y s u r f a c e a r e a ; BUN T, , , = t i m e o n c a r d i o p u l m o n a r y
blood urea nitrogen; bypass or pump time;
N Y
:
pressures retarding fluid flow from the intravascular bed to the extravascular space may be lower in the reperfused lungs of patients in w h o m hemodilufion is greater. Other things being equal, a smaller patient blood volume (or smaller body weight) combined with the constant prime volume of the extracorporeal circuit will necessarily result in a greater degree of hemodilution. This, in turn, alters the balance of the relevant oncotic pressures and favors fluid flow from the intravascular to the extravascular space• As indirect evidence, we found that postoperative hemoglobin levels were generally higher as patient weight increased (Fig 2). Note, however, that other factors such as preoperative hemoglobin level, blood removal, diuresis, urine output, fluids added to the circuit during bypass, perfusion time, and intraoperative transfusions undoubtedly affect the relationship between postoperative hemoglobin level and body weight. Indeed, the interpatient variability of all these factors is probably responsible for the observed variability in postoperative hemoglobin level at any given body weight (see Fig 2). Also consistent with this contention, Magovern and co-workers [9] found that low body surface area and body mass index in CABG patients were predictors of increased postoperative blood transfusions because of decreased blood volume in general and red cells mass in particular. Of the factors implicated with delayed extubation, fluid retention can potentially be manipulated (eg, by hemoconcentration) in a manner that may improve postoperative lung function. Multivariate linear regression analysis applied to the postbypass fluid balance normalized to body surface area indicated that fluid retention was increased with age, in patients with higher preoperative blood urea nitrogen levels, and with time on cardiopulmonary bypass (Table 5). Also, we found that fluid retention was significantly higher for patients in w h o m albumin was not used in the p u m p prime solution. Time on bypass increases with the n u m b e r of grafts (or anastomoses), hypothermia, and redo operation, and can depend on surgeon speed and experience (Table 6). In the univariate analysis, hypothermia was associated with delayed extubation possibly because patient rewarming at the end of bypass increases time on cardiopulmonary
Ann Thorac Surg
HABIB ET AL EARLY EXTUBAT1ONAFTER CORONARY BYPASS
1996;62:1164-71
Table 6. Independent Predictors qf Time on Cardiopuhnonary Bypass Covariate Constant (min) Preop diuretics (Y/N) Redo operation (Y/N) No. of anastomoses 3.T (37°C-LCT) Surgeon ~
Coefficient (a3-a 7)
Standard Error
p Value
0.6 6.0 40.0 11.1 2.21 11.4
3.5 2.5 6.0 0.5 0.42 1.0
... < 0.02 < 0.0001 < 0.0001
,~Four surgeons were assigned numerical values of 0 (fastest), 1, 2, and 3 (slowest); surgeon quickness was determined according to the average time on cardiopulmonarv bypass per graft. LCT ~ lowest core temperature; N . n~; Y yes; ._kT degree of hypothermia. bypass, which, in turn, can i n c r e a s e fluid r e t e n t i o n in the lungs. N o r m o t h e r m i a m a y also r e d u c e the p e r i o d of m e c h a n i c a l v e n t i l a t o r y s u p p o r t in the cardiac surgical p a t i e n t by a v o i d i n g or m i n i m i z i n g the n e e d of active r e w a r m i n g in the i n t e n s i v e care unit (ICU). Pathi a n d c o l l e a g u e s [10] r e c e n t l y r e p o r t e d s h o r t e r T e x t in p a t i e n t s w h o are r e w a r m e d faster in the I C U after h y p o t h e r m i c bypass. This c o u p l e d w i t h the relatively short v e n t i l a t o r y s u p p o r t p e r i o d in o u r C A B G p a t i e n t s (89% h a d n o r m o t h e r m i c c a r d i o p u l m o n a r y bypass) i n d i c a t e s that n o r m o t h e r m i a m a y facilitate earlier extubation. This c o n t e n t i o n is s u p p o r t e d by T o n z a n d associates [11], w h o p r o s p e c tively f o u n d that p a t i e n t s u n d e r g o i n g n o r m o t h e r m i c bypass w e r e e x t u b a t e d earlier t h a n t h o s e h a v i n g h y p o t h e r mic b y p a s s (13.3 v e r s u s 16.4 hours). H o w e v e r , a l t h o u g h c o m p e l l i n g , it is u n c l e a r w h e t h e r the d e c r e a s e in t i m e on c a r d i o p u l m o n a D' b y p a s s e x p e c t e d with n o r m o t h e r m i a will cause a s y s t e m a t i c r e d u c t i o n in the n e t p o s i t i v e fluid b a l a n c e at the e n d of o p e r a t i o n . S t u d i e s d e s i g n e d specifically to a d d r e s s this q u e s t i o n are n e c e s s a r y . Also of i m p o r t w h e n c o n s i d e r i n g the m e t h o d of p e r f u sion is the c o n t r o v e r s y s u r r o u n d i n g the n e u r o p r o t e c t i v e effects of h y p o t h e r m i a c o m p a r e d w i t h n o r m o t h e r m i a [12, 13]. If true, t h e n s u r g e o n s m u s t w e i g h the b e n e f i t s of earlier e x t u b a t i o n v e r s u s the i n c r e a s e d p o t e n t i a l for n e u rologic accidents. In our p r e d o m i n a n t l y n o r m o t h e r m i c e x p e r i e n c e o v e r the last d e c a d e , the i n c i d e n c e of n e u r o logic a c c i d e n t s c o m p a r e s f a v o r a b l y with the n a t i o n a l data. In this C A B G series, 11 (2.1%) of 522 p a t i e n t s s u s t a i n e d n e u r o l o g i c e v e n t s w i t h o n l y a single o p e r a t i v e death. T h e s e n e u r o l o g i c e v e n t s w e r e as follows: six p e r m a n e n t strokes (1.1'%), f o u r t r a n s i e n t strokes (0.8%), a n d one case of c o m a (0.2°,'0). This i n c i d e n c e of central n e r v o u s s y s t e m e v e n t s c o m p a r e s f a v o r a b l y w i t h that rep o r t e d by M c L e a n a n d associates [12] for C A B G p r o c e d u r e s with n o r m o t h e r m i c p e r f u s i o n a n d by C r a v e r a n d c o l l e a g u e s I13] u s i n g h y p o t h e r i n i a . U n l i k e the data of M c L e a n and colleagues, t h o s e of C r a v e r a n d c o a u t h o r s s u g g e s t e d that h y p o t h e r m i c p e r f u s i o n d o e s p r o v i d e a n e u r o p r o t e c t i v e effect. A n o t a b l e difference is that n o r m o t h e r m i c p e r f u s i o n on o u r service is a c c o m p a n i e d w i t h cold c a r d i o p l e g i a as o p p o s e d to the w a r m c a r d i o p l e g i a u s e d for the n o r m o t h e r m i a p a t i e n t s in both t h e s e studies.
1169
In a s t u d y similar to ours, A r o m a n d associates [3] r e p o r t e d that log of age, f e m a l e sex, c o n g e s t i v e h e a r t failure w i t h p r e o p e r a t i v e diuretics, a n d u n s t a b l e a n g i n a w e r e p r e d i c t o r s of late e x t u b a t i o n by m u l t i v a r i a t e analysis. T h e i r results are c o n s i s t e n t w i t h t h o s e of o u r univariate analysis, b u t of t h e s e factors, o n l y o l d e r age p r e d i c t e d late e x t u b a t i o n in o u r m u l t i v a r i a t e m o d e l s . C o m p a r i n g statistical m o d e l s f r o m different s t u d i e s can l e a d to t e n u o u s c o n c l u s i o n s u n l e s s the s a m e v a r i a b l e s are c o n s i d e r e d . W e b e l i e v e that the differing results b e t w e e n o u r s t u d y a n d that of A r o m a n d associates [3] are m o s t l y a c o n s e q u e n c e of the a n a l y s e s used. First, A r o m a n d c o - w o r k e r s d i v i d e d p a t i e n t s into early a n d late g r o u p s on the basis of an a priori c h o s e n v e n t i l a t o r y s u p p o r t p e r i o d of 12 h o u r s as o p p o s e d to the statistical a p p r o a c h u s e d by us (see Fig 1). S e c o n d , a n d m o r e i m p o r t a n t l y , w e a n a l y z e d a l a r g e r n u m b e r of v a r i a b l e s (48 v e r s u s 25). To illustrate, b o t h s t u d i e s f o u n d that e x t u b a t i o n is m o r e likely to be d e l a y e d in f e m a l e patients, but, u n l i k e A r o m a n d associates, w e did not find sex to be an i n d e p e n d e n t p r e d i c t o r of late extubation. W e c o n t e n d that in o u r m u l t i v a r i a t e m o d e l , the effect of f e m a l e sex w a s r e p l a c e d by that of two o t h e r variables, i n c i d e n c e of p o s t o p e r a t i v e b a n k b l o o d t r a n s f u s i o n s (44.1% v e r s u s 15.6%) a n d s m a l l e r p a t i e n t w e i g h t . Both v a r i a b l e s w e r e i n d e p e n d e n t p r e d i c t o r s of late extubation, w e r e m o r e p r e v a l e n t in f e m a l e patients, a n d w e r e not i n c l u d e d in the analysis by A r o m a n d colleagues. Clinical b e n e f i t s of early extubation, especially o n r e s p i r a t o r y a n d c a r d i o v a s c u l a r function, h a v e b e e n des c r i b e d e l s e w h e r e [14-22]. The e c o n o m i c b e n e f i t s of early hospital d i s c h a r g e can also be s u b s t a n t i a l a n d h a v e b e c o m e i n c r e a s i n g l y i m p o r t a n t in the c u r r e n t h e a l t h care e n v i r o n m e n t . Early e x t u b a t i o n has r e c e n t l y b e e n p r e s e n t e d as o n e of the c e n t r a l c o m p o n e n t s of critical p a t h s d e s i g n e d to e x p e d i t e d i s c h a r g e from the I C U a n d the hospital. O u r results are c o n s i s t e n t w i t h this c o n t e n t i o n , as b o t h I C U a n d p o s t o p e r a t i v e h o s p i t a l stays w e r e significantly d e c r e a s e d w i t h early e x t u b a t i o n in this series (Table 7). T h e s e r e d u c t i o n s in I C U a n d p o s t o p e r a t i v e l e n g t h of stay are similar to t h o s e r e p o r t e d by A r o m a n d associates [3], w h o also r e p o r t e d an a v e r a g e d e c r e a s e in
Table 7. Patient Outcome Data for Extubation Groups"
Variable
Early Extubation ( T e x t < 8 h)
Late Extubation (8 h < T,.xt < 24 h)
p Value b
T,,,t (h) CVICU LOS (d) Postop LOS (d) Reintubation (%) ECF (%) Readmission (%)~
5.65 + 1.31 1.06 + 0.37 5.26 *: 1.84 2.8 3.2 10.7
13.7 - 3.4 1.30 - 1.64 6.32 - 3.31 3.5 4.8 10.1
< 0.001 < 0.001 < 0.001 NS NS NS
" Where applicable, data are shown as the mean - the standard error of the mean. b The p values represent results of univariate analysis. • This means readmission to hospital within 6 weeks of discharge. CVICU cardiovascular intensive care unit; ECF extended care facility; LOS length of stay; NS not significant; Tex t = time to extubation.
1170
HABIBET AI, EARLY EXTUBATIONAFTER CORONARY BYPASS
h o s p i t a l c h a r g e s of $6,000 p e r p a t i e n t as a result of early extubation. In s u m m a r y , clinical a n d e c o n o m i c b e n e f i t s of early e x t u b a t i o n are well d o c u m e n t e d . In 1994, early e x t u b a tion w i t h i n 8 h o u r s of I C U a d m i s s i o n was a c c o m p l i s h e d in 51% of o u r p a t i e n t s e v e n t h o u g h e x t u b a t i o n m a y h a v e b e e n artificially p r o l o n g e d in p a t i e n t s w h o r e m a i n e d on mechanical ventilation past midnight. We now routinely e x t u b a t e p a t i e n t s at all h o u r s as s o o n as criteria are met. In o u r e x p e r i e n c e a n d that of o t h e r s [3], early e x t u b a t i o n p e r f o r m e d as s o o n as c a r d i o p u l m o n a r y stability a n d p r o p e r s p o n t a n e o u s v e n t i l a t i o n are e s t a b l i s h e d is a safe practice a n d is not a s s o c i a t e d w i t h i n c r e a s e d risk of r e i n t u b a t i o n or h o s p i t a l r e a d m i s s i o n . I n c r e a s e d age, s m a l l e r p a t i e n t w e i g h t , N e w York H e a r t A s s o c i a t i o n class IV, n u m b e r of a n a s t o m o s e s (or grafts), fluid b a l a n c e n o r m a l i z e d to b o d y surface area, p o s t o p e r a t i v e i n t r a a o r tic b a l l o o n p u m p use, a n d b a n k b l o o d t r a n s f u s i o n s w e r e i n d e p e n d e n t p r e d i c t o r s of p r o l o n g e d m e c h a n i c a l v e n t i lation by r e t r o s p e c t i v e analysis. A m o r e definitive characterization of the role of t h e s e p r e d i c t o r s is b e s t d e t e r m i n e d w i t h future p r o s p e c t i v e studies. Finally, f u r t h e r a n a l y s e s s u g g e s t e d that d e c r e a s i n g fluid r e t e n t i o n (eg, ultrafiltration) a n d d e c r e a s i n g t i m e on b y p a s s (eg, n o r m o t h e r m i a ) m a y r e s u l t in i m p r o v e d p u l m o n a r y function a n d earlier extubation. We thank Donna A. Tenant, RN, and Susan M. Coyle, RN, for their invaluable assistance in data collection, Mike M. Evans, CCP, for help with perfusion data, and Nancy M. Fenn Buderer, MS (statistician), for performing the logistic multivariate analysis. Dr Habib's current address is Department of Pediatrics, Robert Wood Johnson Medical School, 40l Haddon Ave, Camden, NJ 08103.
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Ann Thorac Surg 1996;62:1164-71
6. Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;86:845-57. 7. Ward PA, Till GO, Hatherill JR, Annesley TM, Kunkel RG. Systemic complement activation, lung injury, and products of lipid peroxidation. J Clin Invest 1985;76:512-27. 8. Tennenberg SD, Clardy CW, Bailey WW, Solomkin JS. Complement activation and lung permeability during cardiopulmonary bypass. Ann Thorac Surg 1990;50:597-601. 9. Magovern JA, Sakert T, Benckart DH, et al. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg 1996;61:27-32. 10. Pathi V, Berg GA, Morrison J, Cramp G, McLaren D, Faichhey A. The benefits of active rewarming after cardiac operations: a randomized prospective trial. J Thorac Cardiovasc Surg 1996;111:637-41. 11. Tonz M, Mihaljevic T, yon Segesser LK, Fehr J, Schmid ER, Turina MI. Acute lung injury during cardiopulmonary bypass: are the neutrophils responsible? Chest 1995;108: 1551-6. 12. McLean RF, Wong BI, Naylor D, et al. Cardiopulmonary bypass, temperature, and central nervous system dysfunction. Circulation 1994;90(Suppl 2):250-5. 13. Craver JM, Bufkin BL, Weintraub WS, Guyton RA. Neurologic events after coronary bypass grafting: further observations with warm cardioplegia. Ann Thorac Surg 1995;59: 1429-34. 14. Higgins TL. Pro: early endotracheal extubation is preferable to late extubation in patients following coronary, artery surgery. J Cardiothorac Vasc Anesth 1992;6:488-99. 15. Butler J, Chong GL, Pillai R, Westaby S, Rocker GM. Early extubation after coronary artery bypass surgery: effects on oxygen flux and hemodynamic variables. J Cardiovasc Surg (Torino) 1992;33:276-80. 16. Sackner MA, Hirsch J, Epstein S. Effect of cuffed endotracheal tubes on tracheal mucous velocity. Chest 1975;68: 774-7. 17. Quasha AL, Loeber N, Feeley TW, et al. Postoperative respiratory care: a controlled trial of early and late extubation following coronary artery bypass grafting. Anesthesiology 1980;52:135-41. 18. Jardin F, Fargot JC, Boisante L, eta l. Influence of positive end expiratory pressure on left ventricular performance. N Engl J Med 1981;304:387-92. 19. Boldt J, Kling D, Bormann BV, et al. Influence of PEEP ventilation immediately after cardiopulmonary bypass on right ventricular function. Chest 1988;94:566-71. 20. Guyton RA, Chivarelli M, Padgett CA, et al. The influence of positive end-expiratory pressure on intrapericardial pressure and cardiac function after coronary, bypass surgery. J Cardiothorac Anesth 1987;1:98-107. 21. Prakash O, Simon M, Van der Borden B. Spontaneous ventilation test vs intermittent mandatory, ventilation. Chest 1982;81:403- 6. 22. Gall SA, Olsen CO, Reves JG, et al. Beneficial effects of endotracheal extubation on ventricular performance. J Thorac Cardiovasc Surg 1988;95:819-27.
Ann Thorac Surg 1996;62:1164-71
Appendix 1. Anesthesia and Analgesia Protocols Anesthesia Premedication Lorazepam (Ativan), 2 m g (1 m g if > 70 y or < 60 kg) Induction Diazepam, 2.5-5.0 m g Fentanyl, 10-20 ~ g / k g Pentothal, 0-250 m g to achieve m e a n arterial p r e s s u r e 70 m m Hg P a n c u r o n i u m bromide, 0.1 m g / k g Maintenance Isoflurane, d i a z e p a m (0-7.5 mg), fentanyl (0-5 p.g/kg prn), p a n c u r o n i u m (0.01-0.02 m g / k g prn) (Total doses of d i a z e p a m and fentanyl s h o u l d not exceed 10 m g / k g a n d 30 ~tg/kg) Analgesia Ketorolac (Toradol) 30 m g intravenously on arrival in cardiovascular intensive care unit 30 m g intravenously at first complaint of pain 15-30 m g intravenously every 6 h o u r s (if necessary} If inadequate, s u p p l e m e n t with m o r p h i n e , 0.5-2 m g intravenously p r n Do not use ketorolac if ~70 years, s e r u m creatinine > 1.3 mg/dL, aspirin intolerance
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Appendix 2. Protocol for Weaning Patients From Mechanical Ventilation Obtain chest r o e n t g e n o g r a m , ABG (PaCO2), P~tCO2, and SpO 2 on arrival in cardiovascular intensive care unit PaCO 2 - P~tCO 2 = k If OK with intensivist: Titrate FIO 2 so that S p O 2 > 95% until F10 2 = 30°,; Adjust V T so that PCtCO2 + k 36-40 If change in V~ > 200 mL or PIP > 40, inform intensivist After patient e m e r g e s from anesthesia, decrease IMV by 2/ rain Repeat ABG P 1 C O 2 - P,.t 1CO2 = k ~ If OK with intensivist: Decrease IMV by 2/min to keep PetCO2 <[ PetlCO2 + 3 If ABG and m e c h a n i c s at IMV = 4 m e e t extubation criteria (see Materials a n d M e t h o d s section), t h e n extubate ABG if p r e e x t u b a t i o n PaCO2 > 45 or p o s t e x t u b a t i o n b r e a t h i n g rate >24/rain ABG - arterial blood gases; FIO 2 - inspired oxygen fraction; 1MV - intermittent mandatory ventilation; PaCO~- partial pressure of arterial carbon dioxide from Hg); P~tCO2 = end tidal carbon dioxide; PIP ~ positive inspiratory pressure; SpO 2 oxygen saturation from pulse oximetry; Vt - tidal volume.
Background. Early extubation of cardiac surgical patients enhances ambulation, improves cardiopulmonary function, and can lead to savings in health care costs. Methods. We retrospectively examined the role of 48 variables in determining the period of ventilatory support in 507 patients having coronary artery bypass grafting. Results. Fifteen (<30/o) of 507 patients required ventilatory support in excess of 24 hours. A m o n g the remaining patients, extubation was achieved early (_<8 hours) (mean time, 5.65 - 1.31 hours) in 53% and late (>8 hours) (mean time, 13.7 + 3.4 hours) in 47%. Logistic and linear multivariate regression analyses implicated increased age, N e w York Heart Association functional class IV, intraoperative fluid retention, postoperative intraaortic
balloon pump requirement, and bank blood transfusions as predictors of late extubation. Also, the linear regression linked lower body weight and number of anastomoses (or grafts) to increased mechanical ventilatory support. Conclusions. Analysis of the fluid balance and cardiopulmonary bypass data suggests that earlier extubation may be achieved by actively reducing fluid retention (eg, by hemoconcentration) and time on bypass (eg, normothermia). Finally, intensive care unit stay and postoperative length of stay were significantly lower in the early versus late extubation groups without an increase in pulmonary complications.
~
duration of ventilatory s u p p o r t r e m a i n s highly variable a m o n g patients, a n d studies that systematically explore the causes of this variability are needed. The p r i m a r y goal of this study was to elucidate the patient characteristics a n d operative variables responsible for p r o l o n g e d postoperative respiratory insufficiency in patients u n d e r g o i n g coronary artery bypass grafting (CABG). W e also sought to establish a m o d e l capable of predicting the n e e d of increased postoperative ventilatory s u p p o r t in CABG patients. Arguably, such a m o d e l w o u l d help identify areas of current practice w h e r e modifications might facilitate i m p r o v e d postoperative p u l m o n a r y function.
10r decades, overnight mechanical ventilation was used as s t a n d a r d postoperative care after a cardiac surgical procedure. The rationale for intentionally prolonging ventilatory s u p p o r t was that it m i n i m i z e d episodes of respirato D, insufficiency, hypertension, and patient anxiety [1]. Also, mechanical ventilation decreases the myocardial oxygen d e m a n d s resulting from spontaneous b r e a t h i n g [1]. Recent practice has focused on expediting w e a n i n g from mechanical ventilation. The clinical a d v a n t a g e s of early extubation are mainly that it reduces the possibility of adverse effects of positivepressure ventilation (eg, b a r o t r a u m a ) and minimizes associated patient discomfort, potentially decreases the incidence of infection, and expedites early ambulation. The growing frequency of open heart operations and their high costs have also increased interest in early extubation as a means of reducing intensive care and hospitalization costs [2, 3]. Methods of w e a n i n g cardiac surgical patients from mechanical ventilation continue to evolve a n d can vary greatly a m o n g institutions. Advances in techniques of anesthesia a n d c a r d i o p u l m o n a r y b y p a s s as well as analgesic medications have b e e n i n s t r u m e n t a l in reducing postoperative ventilatory d e p e n d e n c y without increasing the incidence of p u l m o n a r y complications in patients who have u n d e r g o n e an open heart p r o c e d u r e [41. These advances, in turn, have led to appreciable declines in duration of intensive care a n d hospitalization. However,
(Ann Thorac Surg 1996;62:1164-71)
Material a n d M e t h o d s We retrospectively reviewed the case reports of a total of 522 patients who u n d e r w e n t CABG-only p r o c e d u r e s at our institution in 1994. There were six operative deaths (1.1%), and 9 patients (1.7%) had an exceedingly complicated postoperative course with p r o l o n g e d hospitalization (>33 days). These 9 patients were considered outliers as p e r Medicare guidelines a n d were excluded from further analysis. Hence, the study group c o m p r i s e d 507 patients. All patients were o p e r a t e d on a n d cared for by the s a m e group of surgeons, anesthesiologists, a n d cardiovascular intensive care staff.
Perfusion Accepted for publication May 19, 1996. Address reprint requests ~o Dr Zacharias, St. Vincent Medical Center, 2213 Cherry St, ACC 309, Toledo, OH 43608. © 1996 by The Society of Thoracic Surgeons Published bv Elsevier Science Inc
C a r d i o p u l m o n a r y bypass was c o n d u c t e d with an extracorporeal circuit consisting of a m e m b r a n e oxygenator (Baxter Healthcare Corp, Irvine, CA), a centrifugal p u m p 0003-49751961515.00 P[I S0003-4975(96)00565-6
Ann Thorac Surg 1996;62:1164-71
( M e d t r o n i c , Inc, A n a h e i m , CA), a n d t h e c a p a c i t y for u l t r a f i l t r a t i o n . Typically, t h e p u m p w a s p r i m e d w i t h 1,800 m L of P l a s m a l y t e , 50 g of m a n n i t o l (250 mL), a n d 50 g of a l b u m i n (200 mL). O n e s u r g e o n ( s u r g e o n A) d i d n o t u s e a l b u m i n (n = 106 p a t i e n t s ) . N o r m o t h e r m i c (lowest core t e m p e r a t u r e > 3 5 ° C ) p e r f u s i o n w a s u s e d i n t h e m a j o r i t y of p a t i e n t s (89%) w i t h t h e c i r c u i t ' s h e a t e r / c o o l e r t e m p e r a t u r e set at 38°C. M i l d ( l o w e s t core t e m p e r a t u r e = 32 ° to 35°C) h y p o t h e r m i a a n d m o d e r a t e (27°C < l o w e s t c o r e t e m p e r a t u r e < 32°C) h y p o t h e r m i a w e r e u s e d less f r e q u e n t l y (2% a n d 9%, r e s p e c t i v e l y ) . U l t r a f i l t r a t i o n w a s u s e d in a few p a t i e n t s d i a g n o s e d w i t h a n a s a r c a (5/507, 1%). C a r d i o p l e g i a w a s m o s t l y a n t e g r a d e a n d c o n s i s t e d of P l e g i s o l w i t h 1 g of l i d o c a i n e h y d r o c h l o r i d e , 50 m E q of KC1, a n d 15 g of N a H C O 3 (8.4%) in e i t h e r c o l d o x y g e n a t e d c r y s t a l l o i d s o l u t i o n or c o l d b l o o d . A r t e r i a l b l o o d flows w e r e d e t e r m i n e d o n t h e b a s i s of a c a r d i a c i n d e x of 2.5 to 3.0 (L • m i n ~ • m 2), a n d m e a n a r t e r i a l p r e s s u r e s w e r e m a i n t a i n e d b e t w e e n 50 a n d 60 m m Hg.
Anesthesia and Analgesia A n e s t h e s i a a n d a n a l g e s i a w e r e s t a n d a r d i z e d for all p a t i e n t s to m i n i m i z e r e s p i r a t o r y d r i v e a n d t h u s facilitate e a r l i e r e x t u b a t i o n . Briefly, p a t i e n t s w e r e p r e m e d i c a t e d m o s t l y w i t h l o r a z e p a m . A f t e r t h e e s t a b l i s h m e n t of a n a r t e r i a l l i n e a n d a p e r i p h e r a l v e n o u s line, a n e s t h e s i a w a s induced with fentanyl and diazepam. Sodium thiopental (0 to 250 m g ) w a s g i v e n to a c h i e v e a m e a n a r t e r i a l p r e s s u r e of 70 m m Hg. P a n c u r o n i u m b r o m i d e w a s u s e d for m u s c l e r e l a x a t i o n . A f t e r d i r e c t l a r y n g o s c o p y , 4 m L of l i d o c a i n e s o l u t i o n (4%) w a s a p p l i e d to t h e t r a c h e a a n d larynx, a n d t h e p a t i e n t w a s i n t u b a t e d . A n e s t h e s i a a n d muscle relaxation were maintained with isoflurane and s m a l l a d d i t i o n a l d o s e s of f e n t a n y l , d i a z e p a m , a n d p a n c u r o n i u m . T h e t o t a l a m o u n t s of d i a z e p a m a n d f e n t a n y l w e r e c o n t r o l l e d fairly r i g i d l y so as n o t to e x c e e d 10 m g / k g a n d 30 ~ g / k g , r e s p e c t i v e l y . Postoperative analgesia was achieved with ketorolac u n l e s s c o n t r a i n d i c a t e d ( A p p e n d i x 1). C o n t r a i n d i c a t i o n s w e r e a g e g r e a t e r t h a n 70 years, a s e r u m c r e a t i n i n e l e v e l h i g h e r t h a n 1.3 m g / d L , a n d a h i s t o r y of s e n s i t i v i t y to nonsteroid, antiinflammatory drugs. Morphine was used in p a t i e n t s w h e n k e t o r o l a c w a s n o t sufficient. D i a z e p a m a n d h a l o p e r i d o l w e r e u s e d for a n x i o l y s i s a n d a g i t a t i o n , r e s p e c t i v e l y . S m a l l d o s e s (12.5 to 25 m g ) of m e p e r i d i n e h y d r o c h l o r i d e w e r e a d m i n i s t e r e d to r e v e r s e s h i v e r i n g , a n d d o s e s of p a n c u r o n i u m or v e c u r o n i u m b r o m i d e (0.5 to 1 mg) were used when meperidine was inadequate.
Criteria for Extubation Once patients were hemodynamically stable and responsive to c o m m a n d s , v e n t i l a t o r w e a n i n g w a s s t a r t e d as d e s c r i b e d in A p p e n d i x 2 [5]. Briefly, p a t i e n t s w e r e e x t u b a t e d w h e n t h e y m e t s t a n d a r d m e c h a n i c a l f u n c t i o n crit e r i a a n d w e r e a b l e to m a i n t a i n n o r m a l b l o o d g a s e s o n c o n t i n u o u s p o s i t i v e - a i r w a y p r e s s u r e or a n i n t e r m i t t e n t m a n d a t o r y v e n t i l a t i o n r a t e of 4 b r e a t h s / r a i n w i t h a n i n s p i r e d o x y g e n f r a c t i o n of less t h a n or e q u a l to 40%. Standard criteria included an appropriate respiratory rate, t i d a l v o l u m e g r e a t e r t h a n 5 m L / k g , vital c a p a c i t y
HABIB ET AL EARLY EX~fUBATIONAFTER CORONARY BYPASS
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Table 1. Univariate Analysis of Patient Characteristics and Preoperative Data"
Variable Age (y) Weight (kg) BSA (m 2) Preop BUN Preop creatinine Preop hemoglobin Female sex (%) MI (%) Acute MI (%) Unstable angina ('",) Preop IABP (%) CHF (o,) Renal insufficiency (%) Preop diuretics (%) Smoker (%) COPD (%) Obese (%) Diabetes (",.) Insulin dependence (%) Hypercholesterolemia (%) LMD (%) Hypertension (%) Pulmonary hypertension (%) History, of CAD (%) Same-day admission (%) Emergency (%) Redo CABG (%) NYHA class IV (%)
Early Extubation (T,~t < 8 h) (n 259; 52.6%)
Late Extubation (8 h < T~× t -<24 h) (n = 233; 47.4%)
60.2 ÷ 10.0 88.5 + 16.6 2.01 + 0.21 14.8 ÷ 5.2 1.06 -+ 0.72 14.0 _+ 1.45 20.6 56.7 6.0 27.0 3.2 4.0 1.2 12.7 65.9 17.9 17.5 25.8 8.3 66.3 12.7 80.6 1.2
64.7 -+ 10.3 82.1 z 17.2 1.91 ± 0.22 16.1 ± 6.9 1.09 ± 0.68 13.7 ± 1.56 33.0 55.1 8.8 29.1 3.5 8.8 1.8 18.9 64.3 16.3 12.3 32.6 13.2 61.7 14.5 84.1 1.3
63.1 46.8 3.6 3.6 36
67.0 51.4 5.7 2.2 47
p Value b < < < < < < <
0.001 0.001 0.001 0.05 0.07 0.06 0.003 ... ... ... ... < 0.05 ... 0.08 ... ... 0.15 0.12 0.11 ... ... ... ...
... ... ... ... < 0.001
.~Where applicable, data are shown as the mean - the standard deviation. i, Only p values of less than 0.25 in the univariate analysis are reported to indicate variables used in the multivariate analysis. BSA = body surface area; BUN blood urea nitrogen; CABG coronary artery bypass grafting; CAD - coronary artery disease; CHF congestive heart failure; COPD ~ chronic obstructive pulmonarv disease; I A B P intraaortic balloon pump; LMD left main disease; MI - myocardial infarction (acute - less than 24 hours); NYHA New York Heart Association; Te~ t - time to extubation.
g r e a t e r t h a n 10 m L / k g , a n d n e g a t i v e i n s p i r a t o r y force g r e a t e r t h a n 20 m m Hg. T i m e to e x t u b a t i o n (Te×t) o r hours on mechanical ventilation were calculated from t i m e o u t of t h e o p e r a t i n g r o o m , r o u n d e d to t h e c l o s e s t half hour, and recorded.
Statistical Methods P a t i e n t s w e r e d i v i d e d i n t o e a r l y ( T ~ × t < 8 h o u r s ) a n d late (8 < T~×t < 24 h o u r s ) e x t u b a t i o n g r o u p s . T w e n t y - e i g h t p r e o p e r a t i v e ( T a b l e 1), 13 i n t r a o p e r a t i v e , a n d 7 p o s t o p e r a t i v e v a r i a b l e s ( T a b l e 2) w e r e c o m p a r e d . U n i v a r i a t e a n a l y s i s ( S i g m a S t a t ; J a n d e l Scientific, S a n R a p h a e l , C A ) w a s d o n e w i t h X2 or F i s h e r ' s e x a c t t e s t for c a t e g o r i c
1166
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Ann Thorac Surg 1996;62:1164-71
v a r i a b l e s a n d e i t h e r t h e u n p a i r e d t test or t h e n o n p a r a m e t r i c M a n n - W h i t n e y r a n k s u m t e s t for c o n t i n u o u s v a r i ables, d e p e n d i n g o n a p p l i c a b i l i t y . Multivariate analysis was performed with backward e l i m i n a t i o n logistic r e g r e s s i o n s (SAS I n s t i t u t e Inc, C a r y , N C ) a n d s t e p w i s e l i n e a r r e g r e s s i o n s ( S i g m a S t a t ) . For u n i v a r i a t e s i g n i f i c a n c e levels, w e u s e d a p v a l u e of less t h a n 0.25 for c o v a r i a t e i n c l u s i o n a n d a p v a l u e of less t h a n 0.05 for c o v a r i a t e r e t e n t i o n . T h e logistic a n d l i n e a r m o d els p r o v i d e d t h e i n d e p e n d e n t p r e d i c t o r s of a binary.
Table 2. Univariate Analysis of Intraoperative and Postoperative Variables' ,b
Variable lntraoperative Blood removal (mL) No of anastomoses No. of proximal anastomoses No. of grafts/distal anastomoses Pump time (min) Cross-clamp time (rain) LCT (°C) Fluid balance (mL) Fluid balance/BSA (mL/m 2) Postop hemoglobin Surgeon (%) A
B C D Perfusion (%) Normothermia Mild hypothermia Moderate hypothermia Albumin (%) Postoperative Periop IABP (%) Periop MI (%) Bank blood transfusions (",,) Renal failure (%) Neurologic event (%) Postop bleeding (%) Arrhythmia (%) Atrial fibrillation Ventricular fibrillation
Earlv Extubation (T~,x, < 8 h)
Late Extubation (8 h <3 p T~.~t< 24 h) Value"
273 ~ 157 5.02 ~ 1.87 1.98 ± 0.90
244 ÷ 171 5.45 ~ 1.78 2.20 ? 0.87
0.17 < 0.02 <: 0.02
3.02 :~ 1.02
3.22 + 0.97
•: 0.04
88.2 51.8 35.3 1,179 585
~ ~ ~ -
30.8 95.3 + 19.8 54.3 + 1.9 34.8 ~ 1,010 1,448 + 500 762 +
7.42 - 1.61
34.9 <- 0.05 20.6 0.16 2.2 1,041 < 0.005 562 < 0.001
7.18 * 1.39
55 48 55 55
45 52 45 45
90.5 2.8 6.7 77
85.9 1.3 12.8 79
4.0 0.8 14.7
9.3 0.9 32.6
0 0 0.8
1.3 0.4 1.3
0.4 0
1.8 0.4
< 0.02 0.06
• 0.05
< 0.05 < 0.001
0.18
~ Postoperative data were obtained during stay in cardiovascular intensive care unit. b Where applicable, data are shown as the mean + the standard deviation. ~ Only p values of less than 0.25 in the univariate analysis are reported so as to indicate variables used in the multivariate analysis. BSA bodv surface area; LCT lowest core temperature; time to extubation.
IABP intraaortic balloon pump; MI mvocardial infarction; T~,t
(early v e r s u s late) a n d a c o n t i n u o u s (Tex t i n h o u r s ) r e p r e s e n t a t i o n of Text, r e s p e c t i v e l y . T h e t w o t y p e s of m u l t i v a r i a t e a n a l y s i s w e r e u s e d to d e t e r m i n e w h e t h e r a f o r c e d b i n a r y d e s c r i p t i o n of Tex t i n f l u e n c e d t h e r e s u l t s b y e x c l u d i n g i m p o r t a n t or r e t a i n i n g u n i m p o r t a n t i n d e p e n dent predictors or both.
Results F i g u r e 1 i l l u s t r a t e s t h e f r e q u e n c y d i s t r i b u t i o n of Te× t i n 507 C A B G p a t i e n t s . Briefly, 51% of p a t i e n t s w e r e e x t u b a t e d w i t h i n 8 h o u r s ( m e d i a n T~×t = 8 h o u r s ) , a n d less t h a n 3% of p a t i e n t s (15/507) r e q u i r e d v e n t i l a t o r y s u p p o r t for m o r e t h a n 24 h o u r s . In g e n e r a l , t h e p a t i e n t s w e r e d i v i d e d i n t o t w o g r o u p s o n t h e b a s i s of t h e n e a r l y b i m o d a l f r e q u e n c y d i s t r i b u t i o n of Te×t: (1) a n e a r l y e x t u b a t i o n g r o u p (T,,xt < 8 h o u r s , m e d i a n = 5.5 h o u r s , n 259) a n d (2) a late e x t u b a t i o n g r o u p (8 < Tex t G 24, m e d i a n - 13.5 h o u r s , n - 233). P r e o p e r a t i v e d a t a for t h e t w o g r o u p s a r e c o m p a r e d in T a b l e 1. H e r e , t h e r e t r o s p e c t i v e u n i v a r i a t e a n a l y s i s r e v e a l e d t h a t p a t i e n t s in t h e late e x t u b a t i o n g r o u p w e r e a n a v e r a g e of 4.5 y e a r s older, i n c l u d e d m o r e f e m a l e p a t i e n t s (33% v e r s u s 21%), a n d w e r e a n a v e r a g e of 6.4 k g s m a l l e r . Also, p a t i e n t s in t h i s g r o u p w e r e g e n e r a l l y s i c k e r t h a n t h o s e i n t h e e a r l y e x t u b a t i o n g r o u p , as t h e y h a d t w i c e t h e i n c i d e n c e of c o n g e s t i v e h e a r t f a i l u r e (8.8% v e r s u s 4.0%), a h i g h e r p e r c e n t a g e of t h e m w e r e in N e w Y o r k H e a r t A s s o c i a t i o n class IV, a n d t h e p r e o p e r a t i v e b l o o d u r e a nitrogen and creatinine levels were higher. The dec r e a s e d p r e o p e r a t i v e h e m o g l o b i n level, t h e i n c r e a s e d c r e a t i n i n e level, a n d t h e m o r e f r e q u e n t u s e of p r e o p e r a tive d i u r e t i c s in t h e late e x t u b a t i o n g r o u p all a p p r o a c h e d significance. lntraoperative and postoperative data are summarized in T a b l e 2. E l e v e n v a r i a b l e s ( n i n e i n t r a o p e r a t i v e a n d t w o postoperative) differed significantly between the early a n d late e x t u b a t i o n g r o u p s . P a t i e n t s in t h e late g r o u p g e n e r a l l y r e c e i v e d m o r e g r a f t s (3.22 v e r s u s 3.02), a n d total c a r d i o p u l m o n a r y b y p a s s t i m e w a s l o n g e r b y a n a v e r a g e of 7.1 m i n u t e s . A l t h o u g h e m p l o y e d i n o n l y a s m a l l n u m b e r of p a t i e n t s , u s e of m o d e r a t e h y p o t h e r m i a w a s n e a r l y t w i c e as f r e q u e n t for t h e late g r o u p (12.8% v e r s u s 6.7%). Also, a b s o l u t e fluid r e t e n t i o n (liters) calcul a t e d f r o m t h e t o t a l f l u i d i n p u t v e r s u s o u t p u t w a s 22% h i g h e r a f t e r b y p a s s i n t h e late e x t u b a t i o n g r o u p c o m pared with the early extubation group. This difference w a s i n c r e a s e d to 30% w h e n fluid b a l a n c e w a s n o r m a l i z e d to t h e p a t i e n t ' s b o d y s u r f a c e area. O n t h e o t h e r h a n d , h e m o g l o b i n c o n c e n t r a t i o n s w e r e g e n e r a l l y l o w e r for t h e late e x t u b a t i o n g r o u p t h a n t h e e a r l y e x t u b a t i o n g r o u p . P o s t o p e r a t i v e b a n k b l o o d t r a n s f u s i o n s (32.6% v e r s u s 14.7%) a n d u s e of i n t r a a o r t i c b a l l o o n p u m p s (9.3% v e r s u s 4.0%) w e r e m o r e f r e q u e n t in t h e late g r o u p . S e v e r a l of t h e 18 v a r i a b l e s l i n k e d to late e x t u b a t i o n b y u n i v a r i a t e a n a l y s i s are c o r r e l a t e d (eg, n u m b e r s of g r a f t s a n d p e r f u s i o n t i m e ) a n d h e n c e m a y n o t all b e i n d e p e n d e n t p r e d i c t o r s of p r o l o n g e d m e c h a n i c a l v e n t i l a t i o n . Acc o u n t i n g for c o d e p e n d e n c e of v a r i a b l e s , t h e m u l t i v a r i a t e logistic m o d e l i n c l u d e d a t o t a l of five i n d e p e n d e n t p r e -
Ann Thorac Surg 1996;62:1164-71
HABIB ET AL EARLY EXTUBATION AFTER C O R O N A R Y BYPASS
Fig 1. Bimodal frequency distribution of time on ventilatory support in 507 patients undergoing coron a r y artery bypass grafting. D o t t e d l i n e depicts the median time to extubation (T ,~t) of 8 hours, w h i c h also separates the bimodal patient population into early ( w h i t e b a r s ) and late ( b l a c k b a r s ) extubation groups.
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dictors of late extubation (Table 3). These were older age, N e w York Heart Association class IV, increased positive fluid balance normalized to body surface area, use of postoperative intraaortic balloon pump, and bank blood transfusions. In addition to these five variables, the stepwise multivariate linear regression analysis also implicated smaller patient weight and increased number of anastomoses or grafts as predictors of increased Te× t (Table 4). Besides avoiding categorizing patients into groups (ie, late and early), the linear model also permitted a more straightforward interpretation of the relative impact of each of the predictors of Text. For instance, all else being equal, the linear model coefficient estimated for age (0.06) translates to an average increase of 0.6 hour in mechanical ventilation for every 10-year increase in patient age. S i m i l a r l y , Te× t is expected to increase by I hour for every 1 L/m 2 increase in fluid retention. On the other hand, postoperative intraaortic balloon pump use and blood transfusions (categoric variables), when indicated, inc r e a s e T~× t by 2.92 and 1.3 hours, respectively.
open heart operation, to early extubation is a delicate process involving a collaborative effort from surgeons, anesthesiologists, and intensive care staff. In our experience, implementation of early extubation has been a dynamic process that continues to evolve as the medical team providing patient care becomes more experienced. The main goals of this study were to identify the patient characteristics and operative variables that distinguish early extubation and late extubation patient groups, to build a model capable of predicting delayed extubation in CABG patients, and to identify and explore possible areas of surgical and medical practice where modifications may allow earlier extubation. Four of the seven factors implicated by the retrospective multivariate analysis have a direct impact on postoperative recovery. Of these, increased age, N e w York Heart Association class IV, and more frequent blood transfusions indicate a weaker or sicker patient, and increased postoperative use of the intraaortic balloon
Table 4. Independent Predictors of the Continuous Variable Time to Extubation by Stepwise Multivariate Linear Regression Analysis
Comment The change in practice from intentionally prolonged ventilation, advocated for decades for patients having an
Table 3. Independent Predictors of Early Versus Late Extubation by Multivariate Logistic Regression Analysis
Covariate
Odds Ratio
p Value
A g e (y)
1.035
1,02 to 1.06
< 0.0001
N Y H A IV ( Y / N )
1.634
1,10 to 2.43
0.02
Fluid balance/BSA ( m L / m 2)
1.001
1.000 to 1,001
<- 0.0001
Periop IABP (Y/N)
2.551
1.10 to 5.92
0.03
Bank blood transfusions (Y/N)
2.412
1.48 to 3.94
<- 0.0001
N
Standard Error
p Value
Constant (hi b
5.82
1.97
...
A g e (y)
0.06
0.02
0.005
W e i g h t (kg)
95% Confidence Interval
BSA = b o d y surface area; IABP = intraaortic balloon p u m p ; no; NYHA :: New York Heart Association; Y yes.
Coefficient" (al-a7)
Covariate
-0.03
0.01
0.01
N Y H A c l a s s IV ( Y / N )
1.00
0.42
0.02
No. of anastomoses
0.24
0.11
0.04
0.001
0.0004
0.01
Periop IABP (Y/N)
2.92
1.04
0.005
Bank blood transfusions
1.30
0.52
0.01
Fluid balance/BSA
( m L / m 2)
" Positive/negative coefficient values indicate increased time to extubation (in hours) with increased~decreased value of numerical variables or incidence/absence of categoric variables. 6 Constant is the additive quanti~" in the multiple linear regression model: Time to extubation = a~ x age + a 2 ?K weight 4- a 3 × NYHA class IV + a 4 x anastomoses + a5 × fluid balance normalized to BSA 4- a~, × periop IABP + a7 × b a n k blood transfusion ~ constant, BSA no;
b o d y surface area; IABP intraaortic balloon pump; NYHA - N e w York H e a r t Association; Y yes.
N -
1168
HABIB ET AL EARLY EXTUBATION
AFTER
CORONARY
Ann Thorac Surg 1996;62:1164-71
BYPASS
p u m p indicates persistent hemodvnamic instability and left ventricular dysfunction. Intraoperative fluid retention associated with cardiopulmonary bypass can lead to substantial lung dysfunction [6-8]. A major component of the positive fluid balance retained by the patient at the end of operation is in the form of increased extravascular lung water. Obviously, such pulmonary edema can impair pulmonary function by its deleterious effects on lung mechanics and gas exchange. Extravascular lung water can be further increased in the early postoperative hours after pulmonary reperfusion commences [6]. Movement of fluid between the intravascular and extravascular spaces of the lung can depend on both the degree of hemodilution, through its effects on oncotic pressures, and the endothelial integrity, of the pulmonary vasculature [6]. The linear regression analysis provided evidence in support of this notion (see Table 4). Here, analysis of the time on mechanical ventilation as a continuous variable implicated two additional factors: n u m b e r of anastomoses and patient weight. Time on cardiopulmonary bypass increases with the n u m b e r of grafts (or anastomoses) and has been shown to cause endothelial injury, which increases permeability of the pulmonary vasculature [6-8]. This p h e n o m e n o n has been linked to complement activation and release of inflammatory mediators subsequent to the exposure of blood (leukocytes) to the surface of the extracorporeal circuit during bypass [6-8]. We speculate that decreased patient body weight has an indirect impact on postoperative lung function through its role in fluid retention. To explain this contention, we suggest the following scenario: The oncotic
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Fig 2. Tendcncy.ti}r increased postoperative hemoglobin concentration (inversely related to hemodilution) to be a hmction qfi increased patient body weight. Dots are individual patient data. Squares are averaged data over a range qf patient body weights. Lines represent linear regressions (solid line) (r 0.47), 95% confidence inte~,als (broken lines), and prediction inte~,al (dash-dot lines)•
Table 5. Independent Predictors of Fluid Balance Normalized to Body Surface Area
Covariate Constant (mL/m2)•' Age (y) BUN T..... {rain) Albumin (Y/N)
Coefficient (a i-a=) 186 5.83 10.2 1.81 253
Standard Error
p Value
168 2.44 4.08 0•80 63
... 0.02 0.01 0.02 < 0.0001
-' C o n s t a n t is t h e a d d i t i v e q u a n t i t ) in the multiple linear regression model: Fluid balance normalized t o B S A = a I x a g e + a z × B U N 4 a~ × "1~ Pt* + a4 ~ a l b u m i n + c o n s t a n t . BSA no; ves.
=, b o d y s u r f a c e a r e a ; BUN T, , , = t i m e o n c a r d i o p u l m o n a r y
blood urea nitrogen; bypass or pump time;
N Y
:
pressures retarding fluid flow from the intravascular bed to the extravascular space may be lower in the reperfused lungs of patients in w h o m hemodilufion is greater. Other things being equal, a smaller patient blood volume (or smaller body weight) combined with the constant prime volume of the extracorporeal circuit will necessarily result in a greater degree of hemodilution. This, in turn, alters the balance of the relevant oncotic pressures and favors fluid flow from the intravascular to the extravascular space• As indirect evidence, we found that postoperative hemoglobin levels were generally higher as patient weight increased (Fig 2). Note, however, that other factors such as preoperative hemoglobin level, blood removal, diuresis, urine output, fluids added to the circuit during bypass, perfusion time, and intraoperative transfusions undoubtedly affect the relationship between postoperative hemoglobin level and body weight. Indeed, the interpatient variability of all these factors is probably responsible for the observed variability in postoperative hemoglobin level at any given body weight (see Fig 2). Also consistent with this contention, Magovern and co-workers [9] found that low body surface area and body mass index in CABG patients were predictors of increased postoperative blood transfusions because of decreased blood volume in general and red cells mass in particular. Of the factors implicated with delayed extubation, fluid retention can potentially be manipulated (eg, by hemoconcentration) in a manner that may improve postoperative lung function. Multivariate linear regression analysis applied to the postbypass fluid balance normalized to body surface area indicated that fluid retention was increased with age, in patients with higher preoperative blood urea nitrogen levels, and with time on cardiopulmonary bypass (Table 5). Also, we found that fluid retention was significantly higher for patients in w h o m albumin was not used in the p u m p prime solution. Time on bypass increases with the n u m b e r of grafts (or anastomoses), hypothermia, and redo operation, and can depend on surgeon speed and experience (Table 6). In the univariate analysis, hypothermia was associated with delayed extubation possibly because patient rewarming at the end of bypass increases time on cardiopulmonary
Ann Thorac Surg
HABIB ET AL EARLY EXTUBAT1ONAFTER CORONARY BYPASS
1996;62:1164-71
Table 6. Independent Predictors qf Time on Cardiopuhnonary Bypass Covariate Constant (min) Preop diuretics (Y/N) Redo operation (Y/N) No. of anastomoses 3.T (37°C-LCT) Surgeon ~
Coefficient (a3-a 7)
Standard Error
p Value
0.6 6.0 40.0 11.1 2.21 11.4
3.5 2.5 6.0 0.5 0.42 1.0
... < 0.02 < 0.0001 < 0.0001
,~Four surgeons were assigned numerical values of 0 (fastest), 1, 2, and 3 (slowest); surgeon quickness was determined according to the average time on cardiopulmonarv bypass per graft. LCT ~ lowest core temperature; N . n~; Y yes; ._kT degree of hypothermia. bypass, which, in turn, can i n c r e a s e fluid r e t e n t i o n in the lungs. N o r m o t h e r m i a m a y also r e d u c e the p e r i o d of m e c h a n i c a l v e n t i l a t o r y s u p p o r t in the cardiac surgical p a t i e n t by a v o i d i n g or m i n i m i z i n g the n e e d of active r e w a r m i n g in the i n t e n s i v e care unit (ICU). Pathi a n d c o l l e a g u e s [10] r e c e n t l y r e p o r t e d s h o r t e r T e x t in p a t i e n t s w h o are r e w a r m e d faster in the I C U after h y p o t h e r m i c bypass. This c o u p l e d w i t h the relatively short v e n t i l a t o r y s u p p o r t p e r i o d in o u r C A B G p a t i e n t s (89% h a d n o r m o t h e r m i c c a r d i o p u l m o n a r y bypass) i n d i c a t e s that n o r m o t h e r m i a m a y facilitate earlier extubation. This c o n t e n t i o n is s u p p o r t e d by T o n z a n d associates [11], w h o p r o s p e c tively f o u n d that p a t i e n t s u n d e r g o i n g n o r m o t h e r m i c bypass w e r e e x t u b a t e d earlier t h a n t h o s e h a v i n g h y p o t h e r mic b y p a s s (13.3 v e r s u s 16.4 hours). H o w e v e r , a l t h o u g h c o m p e l l i n g , it is u n c l e a r w h e t h e r the d e c r e a s e in t i m e on c a r d i o p u l m o n a D' b y p a s s e x p e c t e d with n o r m o t h e r m i a will cause a s y s t e m a t i c r e d u c t i o n in the n e t p o s i t i v e fluid b a l a n c e at the e n d of o p e r a t i o n . S t u d i e s d e s i g n e d specifically to a d d r e s s this q u e s t i o n are n e c e s s a r y . Also of i m p o r t w h e n c o n s i d e r i n g the m e t h o d of p e r f u sion is the c o n t r o v e r s y s u r r o u n d i n g the n e u r o p r o t e c t i v e effects of h y p o t h e r m i a c o m p a r e d w i t h n o r m o t h e r m i a [12, 13]. If true, t h e n s u r g e o n s m u s t w e i g h the b e n e f i t s of earlier e x t u b a t i o n v e r s u s the i n c r e a s e d p o t e n t i a l for n e u rologic accidents. In our p r e d o m i n a n t l y n o r m o t h e r m i c e x p e r i e n c e o v e r the last d e c a d e , the i n c i d e n c e of n e u r o logic a c c i d e n t s c o m p a r e s f a v o r a b l y with the n a t i o n a l data. In this C A B G series, 11 (2.1%) of 522 p a t i e n t s s u s t a i n e d n e u r o l o g i c e v e n t s w i t h o n l y a single o p e r a t i v e death. T h e s e n e u r o l o g i c e v e n t s w e r e as follows: six p e r m a n e n t strokes (1.1'%), f o u r t r a n s i e n t strokes (0.8%), a n d one case of c o m a (0.2°,'0). This i n c i d e n c e of central n e r v o u s s y s t e m e v e n t s c o m p a r e s f a v o r a b l y w i t h that rep o r t e d by M c L e a n a n d associates [12] for C A B G p r o c e d u r e s with n o r m o t h e r m i c p e r f u s i o n a n d by C r a v e r a n d c o l l e a g u e s I13] u s i n g h y p o t h e r i n i a . U n l i k e the data of M c L e a n and colleagues, t h o s e of C r a v e r a n d c o a u t h o r s s u g g e s t e d that h y p o t h e r m i c p e r f u s i o n d o e s p r o v i d e a n e u r o p r o t e c t i v e effect. A n o t a b l e difference is that n o r m o t h e r m i c p e r f u s i o n on o u r service is a c c o m p a n i e d w i t h cold c a r d i o p l e g i a as o p p o s e d to the w a r m c a r d i o p l e g i a u s e d for the n o r m o t h e r m i a p a t i e n t s in both t h e s e studies.
1169
In a s t u d y similar to ours, A r o m a n d associates [3] r e p o r t e d that log of age, f e m a l e sex, c o n g e s t i v e h e a r t failure w i t h p r e o p e r a t i v e diuretics, a n d u n s t a b l e a n g i n a w e r e p r e d i c t o r s of late e x t u b a t i o n by m u l t i v a r i a t e analysis. T h e i r results are c o n s i s t e n t w i t h t h o s e of o u r univariate analysis, b u t of t h e s e factors, o n l y o l d e r age p r e d i c t e d late e x t u b a t i o n in o u r m u l t i v a r i a t e m o d e l s . C o m p a r i n g statistical m o d e l s f r o m different s t u d i e s can l e a d to t e n u o u s c o n c l u s i o n s u n l e s s the s a m e v a r i a b l e s are c o n s i d e r e d . W e b e l i e v e that the differing results b e t w e e n o u r s t u d y a n d that of A r o m a n d associates [3] are m o s t l y a c o n s e q u e n c e of the a n a l y s e s used. First, A r o m a n d c o - w o r k e r s d i v i d e d p a t i e n t s into early a n d late g r o u p s on the basis of an a priori c h o s e n v e n t i l a t o r y s u p p o r t p e r i o d of 12 h o u r s as o p p o s e d to the statistical a p p r o a c h u s e d by us (see Fig 1). S e c o n d , a n d m o r e i m p o r t a n t l y , w e a n a l y z e d a l a r g e r n u m b e r of v a r i a b l e s (48 v e r s u s 25). To illustrate, b o t h s t u d i e s f o u n d that e x t u b a t i o n is m o r e likely to be d e l a y e d in f e m a l e patients, but, u n l i k e A r o m a n d associates, w e did not find sex to be an i n d e p e n d e n t p r e d i c t o r of late extubation. W e c o n t e n d that in o u r m u l t i v a r i a t e m o d e l , the effect of f e m a l e sex w a s r e p l a c e d by that of two o t h e r variables, i n c i d e n c e of p o s t o p e r a t i v e b a n k b l o o d t r a n s f u s i o n s (44.1% v e r s u s 15.6%) a n d s m a l l e r p a t i e n t w e i g h t . Both v a r i a b l e s w e r e i n d e p e n d e n t p r e d i c t o r s of late extubation, w e r e m o r e p r e v a l e n t in f e m a l e patients, a n d w e r e not i n c l u d e d in the analysis by A r o m a n d colleagues. Clinical b e n e f i t s of early extubation, especially o n r e s p i r a t o r y a n d c a r d i o v a s c u l a r function, h a v e b e e n des c r i b e d e l s e w h e r e [14-22]. The e c o n o m i c b e n e f i t s of early hospital d i s c h a r g e can also be s u b s t a n t i a l a n d h a v e b e c o m e i n c r e a s i n g l y i m p o r t a n t in the c u r r e n t h e a l t h care e n v i r o n m e n t . Early e x t u b a t i o n has r e c e n t l y b e e n p r e s e n t e d as o n e of the c e n t r a l c o m p o n e n t s of critical p a t h s d e s i g n e d to e x p e d i t e d i s c h a r g e from the I C U a n d the hospital. O u r results are c o n s i s t e n t w i t h this c o n t e n t i o n , as b o t h I C U a n d p o s t o p e r a t i v e h o s p i t a l stays w e r e significantly d e c r e a s e d w i t h early e x t u b a t i o n in this series (Table 7). T h e s e r e d u c t i o n s in I C U a n d p o s t o p e r a t i v e l e n g t h of stay are similar to t h o s e r e p o r t e d by A r o m a n d associates [3], w h o also r e p o r t e d an a v e r a g e d e c r e a s e in
Table 7. Patient Outcome Data for Extubation Groups"
Variable
Early Extubation ( T e x t < 8 h)
Late Extubation (8 h < T,.xt < 24 h)
p Value b
T,,,t (h) CVICU LOS (d) Postop LOS (d) Reintubation (%) ECF (%) Readmission (%)~
5.65 + 1.31 1.06 + 0.37 5.26 *: 1.84 2.8 3.2 10.7
13.7 - 3.4 1.30 - 1.64 6.32 - 3.31 3.5 4.8 10.1
< 0.001 < 0.001 < 0.001 NS NS NS
" Where applicable, data are shown as the mean - the standard error of the mean. b The p values represent results of univariate analysis. • This means readmission to hospital within 6 weeks of discharge. CVICU cardiovascular intensive care unit; ECF extended care facility; LOS length of stay; NS not significant; Tex t = time to extubation.
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HABIBET AI, EARLY EXTUBATIONAFTER CORONARY BYPASS
h o s p i t a l c h a r g e s of $6,000 p e r p a t i e n t as a result of early extubation. In s u m m a r y , clinical a n d e c o n o m i c b e n e f i t s of early e x t u b a t i o n are well d o c u m e n t e d . In 1994, early e x t u b a tion w i t h i n 8 h o u r s of I C U a d m i s s i o n was a c c o m p l i s h e d in 51% of o u r p a t i e n t s e v e n t h o u g h e x t u b a t i o n m a y h a v e b e e n artificially p r o l o n g e d in p a t i e n t s w h o r e m a i n e d on mechanical ventilation past midnight. We now routinely e x t u b a t e p a t i e n t s at all h o u r s as s o o n as criteria are met. In o u r e x p e r i e n c e a n d that of o t h e r s [3], early e x t u b a t i o n p e r f o r m e d as s o o n as c a r d i o p u l m o n a r y stability a n d p r o p e r s p o n t a n e o u s v e n t i l a t i o n are e s t a b l i s h e d is a safe practice a n d is not a s s o c i a t e d w i t h i n c r e a s e d risk of r e i n t u b a t i o n or h o s p i t a l r e a d m i s s i o n . I n c r e a s e d age, s m a l l e r p a t i e n t w e i g h t , N e w York H e a r t A s s o c i a t i o n class IV, n u m b e r of a n a s t o m o s e s (or grafts), fluid b a l a n c e n o r m a l i z e d to b o d y surface area, p o s t o p e r a t i v e i n t r a a o r tic b a l l o o n p u m p use, a n d b a n k b l o o d t r a n s f u s i o n s w e r e i n d e p e n d e n t p r e d i c t o r s of p r o l o n g e d m e c h a n i c a l v e n t i lation by r e t r o s p e c t i v e analysis. A m o r e definitive characterization of the role of t h e s e p r e d i c t o r s is b e s t d e t e r m i n e d w i t h future p r o s p e c t i v e studies. Finally, f u r t h e r a n a l y s e s s u g g e s t e d that d e c r e a s i n g fluid r e t e n t i o n (eg, ultrafiltration) a n d d e c r e a s i n g t i m e on b y p a s s (eg, n o r m o t h e r m i a ) m a y r e s u l t in i m p r o v e d p u l m o n a r y function a n d earlier extubation. We thank Donna A. Tenant, RN, and Susan M. Coyle, RN, for their invaluable assistance in data collection, Mike M. Evans, CCP, for help with perfusion data, and Nancy M. Fenn Buderer, MS (statistician), for performing the logistic multivariate analysis. Dr Habib's current address is Department of Pediatrics, Robert Wood Johnson Medical School, 40l Haddon Ave, Camden, NJ 08103.
References 1. Lefemine AA, Harken DE. Postoperative care following open heart operations: routine use of controlled ventilation. J Thorac Cardiovasc Surg 1966;52:207-16. 2. Jones EL, Weintraub WS, Craver JM, Guyton RA, Cohen CL. Coronary bypass surgery. Is the operation different today? J Thorac Cardiovasc Surg 1991;101:1080-5. 3. Arom KV, Emery RW, Petersen RJ, Schwartz M. Costeffectiveness and predictors of e a r n extubation. Ann Thorac Surg 1995;60:127-32. 4. Shapiro BA. Inhalation-based anesthesia techniques are the key to early extubation of the cardiac surgery patient. J Cardiothorac Vasc Anesth 1993;7:135-6. 5. Engoren M. Efficacy of capnometry in ventilator, management of cardiac patients. J Cardiothorac Vasc Anesth 1993;7: 538-40.
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6. Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983;86:845-57. 7. Ward PA, Till GO, Hatherill JR, Annesley TM, Kunkel RG. Systemic complement activation, lung injury, and products of lipid peroxidation. J Clin Invest 1985;76:512-27. 8. Tennenberg SD, Clardy CW, Bailey WW, Solomkin JS. Complement activation and lung permeability during cardiopulmonary bypass. Ann Thorac Surg 1990;50:597-601. 9. Magovern JA, Sakert T, Benckart DH, et al. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg 1996;61:27-32. 10. Pathi V, Berg GA, Morrison J, Cramp G, McLaren D, Faichhey A. The benefits of active rewarming after cardiac operations: a randomized prospective trial. J Thorac Cardiovasc Surg 1996;111:637-41. 11. Tonz M, Mihaljevic T, yon Segesser LK, Fehr J, Schmid ER, Turina MI. Acute lung injury during cardiopulmonary bypass: are the neutrophils responsible? Chest 1995;108: 1551-6. 12. McLean RF, Wong BI, Naylor D, et al. Cardiopulmonary bypass, temperature, and central nervous system dysfunction. Circulation 1994;90(Suppl 2):250-5. 13. Craver JM, Bufkin BL, Weintraub WS, Guyton RA. Neurologic events after coronary bypass grafting: further observations with warm cardioplegia. Ann Thorac Surg 1995;59: 1429-34. 14. Higgins TL. Pro: early endotracheal extubation is preferable to late extubation in patients following coronary, artery surgery. J Cardiothorac Vasc Anesth 1992;6:488-99. 15. Butler J, Chong GL, Pillai R, Westaby S, Rocker GM. Early extubation after coronary artery bypass surgery: effects on oxygen flux and hemodynamic variables. J Cardiovasc Surg (Torino) 1992;33:276-80. 16. Sackner MA, Hirsch J, Epstein S. Effect of cuffed endotracheal tubes on tracheal mucous velocity. Chest 1975;68: 774-7. 17. Quasha AL, Loeber N, Feeley TW, et al. Postoperative respiratory care: a controlled trial of early and late extubation following coronary artery bypass grafting. Anesthesiology 1980;52:135-41. 18. Jardin F, Fargot JC, Boisante L, eta l. Influence of positive end expiratory pressure on left ventricular performance. N Engl J Med 1981;304:387-92. 19. Boldt J, Kling D, Bormann BV, et al. Influence of PEEP ventilation immediately after cardiopulmonary bypass on right ventricular function. Chest 1988;94:566-71. 20. Guyton RA, Chivarelli M, Padgett CA, et al. The influence of positive end-expiratory pressure on intrapericardial pressure and cardiac function after coronary, bypass surgery. J Cardiothorac Anesth 1987;1:98-107. 21. Prakash O, Simon M, Van der Borden B. Spontaneous ventilation test vs intermittent mandatory, ventilation. Chest 1982;81:403- 6. 22. Gall SA, Olsen CO, Reves JG, et al. Beneficial effects of endotracheal extubation on ventricular performance. J Thorac Cardiovasc Surg 1988;95:819-27.
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Appendix 1. Anesthesia and Analgesia Protocols Anesthesia Premedication Lorazepam (Ativan), 2 m g (1 m g if > 70 y or < 60 kg) Induction Diazepam, 2.5-5.0 m g Fentanyl, 10-20 ~ g / k g Pentothal, 0-250 m g to achieve m e a n arterial p r e s s u r e 70 m m Hg P a n c u r o n i u m bromide, 0.1 m g / k g Maintenance Isoflurane, d i a z e p a m (0-7.5 mg), fentanyl (0-5 p.g/kg prn), p a n c u r o n i u m (0.01-0.02 m g / k g prn) (Total doses of d i a z e p a m and fentanyl s h o u l d not exceed 10 m g / k g a n d 30 ~tg/kg) Analgesia Ketorolac (Toradol) 30 m g intravenously on arrival in cardiovascular intensive care unit 30 m g intravenously at first complaint of pain 15-30 m g intravenously every 6 h o u r s (if necessary} If inadequate, s u p p l e m e n t with m o r p h i n e , 0.5-2 m g intravenously p r n Do not use ketorolac if ~70 years, s e r u m creatinine > 1.3 mg/dL, aspirin intolerance
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Appendix 2. Protocol for Weaning Patients From Mechanical Ventilation Obtain chest r o e n t g e n o g r a m , ABG (PaCO2), P~tCO2, and SpO 2 on arrival in cardiovascular intensive care unit PaCO 2 - P~tCO 2 = k If OK with intensivist: Titrate FIO 2 so that S p O 2 > 95% until F10 2 = 30°,; Adjust V T so that PCtCO2 + k 36-40 If change in V~ > 200 mL or PIP > 40, inform intensivist After patient e m e r g e s from anesthesia, decrease IMV by 2/ rain Repeat ABG P 1 C O 2 - P,.t 1CO2 = k ~ If OK with intensivist: Decrease IMV by 2/min to keep PetCO2 <[ PetlCO2 + 3 If ABG and m e c h a n i c s at IMV = 4 m e e t extubation criteria (see Materials a n d M e t h o d s section), t h e n extubate ABG if p r e e x t u b a t i o n PaCO2 > 45 or p o s t e x t u b a t i o n b r e a t h i n g rate >24/rain ABG - arterial blood gases; FIO 2 - inspired oxygen fraction; 1MV - intermittent mandatory ventilation; PaCO~- partial pressure of arterial carbon dioxide from Hg); P~tCO2 = end tidal carbon dioxide; PIP ~ positive inspiratory pressure; SpO 2 oxygen saturation from pulse oximetry; Vt - tidal volume.