- Email: [email protected]
A 2-minute pre-extubation protocol for ventilated intensive care unit patients
The American Journal of Surgery (2008) 196, 890 – 895
The Southwestern Surgical Congress
A 2-minute pre-extubation protocol for ventilated intensive care unit patients Abraham Avi Nisim, M.D., Daniel R. Margulies, M.D.*, Matthew T. Wilson, M.D., Rodrigo F. Alban, M.D., Catherine M. Dang, M.D., Alexander D. Allins, M.D., M. Michael Shabot, M.D. Trauma Surgery and Surgical Critical Care, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Suite 8215, Los Angeles, CA 90048, USA KEYWORDS: Extubation; Reintubation; Ventilator weaning
Abstract BACKGROUND: Clinicians often are challenged with safely predicting the optimal time of extubation for ventilated patients. Commonly used weaning parameters have poor positive predictive value for successful extubation. METHODS: A total of 213 intubated patients in our 20-bed surgical intensive care unit were enrolled in a trial to test a prospective, observational, 2-minute extubation protocol (TMEP). Daily measurements were obtained on all intubated patients who met criteria, which included adequate oxygenation, systolic blood pressure, heart rate, hemoglobin, Glasgow Coma Score greater than 10t, absence of significant metabolic/respiratory acidosis, and absence of therapeutic or neurologic paralysis. During TMEP, endotracheally intubated patients were physically disconnected from the ventilator for a 2-minute period of observation while spontaneously breathing room air. Patients were extubated if they tolerated the trial without clinically significant desaturation or alteration of vital signs or mental status. RESULTS: The TMEP reliably predicted successful extubations in 203 of 213 patients (95.3%). Patients who required reintubation had a longer intensive care unit stay and a longer hospital stay. CONCLUSIONS: TMEP is a simple and reliable method of predicting successful extubation. © 2008 Elsevier Inc. All rights reserved.
Discontinuing mechanical ventilation has long been more of an art than a science. With the widespread use of positive-pressure mechanical ventilation via endotracheal tubes, numerous potential complications exist including ventilator-associated pneumonia, tracheal stenosis, vocal cord paresis, and ventilator-induced lung injury.1– 6 Consequently, one of the goals of modern intensive care unit
* Corresponding author: Tel.: ⫹1-310-423-5874; fax: ⫹1-310-4230139. E-mail address: [email protected] Manuscript received May 3, 2008; revised manuscript July 3, 2008
0002-9610/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2008.07.038
(ICU) management is to discontinue mechanical ventilation as quickly and safely as possible. Before the discontinuation of mechanical ventilation, all ventilatory and nonventilatory issues that necessitated mechanical ventilation should be corrected.7 These include gas exchange abnormalities, loss of central respiratory drive as a result of stroke or metabolic derangement, and ventilatory muscle fatigue as a result of mismatched ventilatory demand. To determine when ventilator weaning should be initiated, objective measurements such as adequate oxygenation (PaO2 ⱖ 60 mm Hg on a fraction of inspired oxygen ⱕ 40%, positive end-expiratory pressure ⱕ 8 cm H2O), systolic blood pressure greater than 90 mm Hg, heart rate (HR)
A.A. Nisim et al.
TMEP for ICU patients
greater than 60 bpm, absence of significant metabolic/respiratory acidosis (pH ⱖ 7.25), adequate hemoglobin level (8 –10 g/dL), and adequate mentation (Glasgow Coma Score ⱖ 13), and spontaneous breathing also should be confirmed.7 In a randomized controlled trial, Kollef et al8 showed that traditional physician-directed discontinuation of mechanical ventilation is associated with increased duration of mechanical ventilation and cost when compared with protocol-directed ventilator weaning. Therefore, a simple, reproducible, highly specific, and sensitive test for discontinuing mechanical ventilation is needed. The commonly used weaning parameters have not been proven to definitively predict extubation outcome. In a prospective study of 64 patients, minute ventilation greater than 10 L failed to predict successful extubation in 40% of patients.9 Likewise, negative inspiratory force (NIF) and maximal inspiratory pressure greater than ⫺20 cm H2O have poor positive predictive value, although they appear to have greater utility in predicting unsuccessful discontinuation of ventilatory support.9 –11 Even the rapid shallow breathing index (respiratory rate/tidal volume ratio, ⬍105 /L) has a specificity of only 64%.9,12,13 Consequently, we sought to identify a simple bedside method to predict extubation outcome. We hypothesized that successful completion of a 2-minute spontaneous breathing trial on room air off the ventilator would predict successful discontinuation of mechanical ventilation.
891 The TMEP was performed by physically disconnecting the patient from the ventilator while remaining endotracheally intubated for a 2-minute period of observation. During that time, the patient spontaneously breathed room air and was monitored continuously for distress or changes in hemodynamics or ventilatory status. The decision to extubate were made either as part of morning rounds by the ICU team, which included attendings, fellows, and surgical residents, or at any time when the patients met criteria for an extubation trial by any individual on the ICU team at bedside. Evaluating physicians remained at the bedside observing the patient throughout the trial. At the end of the 2-minute trial (or earlier if the patient became unstable) the patient was reconnected to the ventilator. Patients were extubated if they tolerated the trial without distress, with hemodynamic and respiratory stability, respiratory rate of less than 30, and saturation greater than 90%. Data collection included patient demographics, diagnosis, pulmonary disease, Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS), basal metabolic index, total ICU length of stay (LOS), and hospital LOS. Pre-TMEP and end-of-trial blood pressure, HR, RR, and percentage of saturation were recorded. A pretrial arterial blood gas also was obtained. A successful trial was defined as any patient who did not require reintubation within 24 hours of extubation.
Statistical analysis
Patients and Methods This prospective observational study was conducted in an urban 951-bed Level I trauma and multi-organ transplant center. Intubated patients cared for in a 20-bed surgical ICU (SICU) from January 1 to December 31, 2005, were included. Patients undergoing cardiac and thoracic procedures were cared for in a different ICU and were not included in this study. The population was a convenience sample of patients with complete data. The study protocol was approved by the Institutional Review Board at Cedars-Sinai Medical Center. Daily physiologic measurements were obtained on all intubated patients who were hemodynamically stable (systolic blood pressure ⬎ 90 mm Hg, 10 ⬍ respiratory rate [RR] ⬍ 30, 60 ⬍ HR ⬍ 110 bpm), GCS greater than 10 t (intubated), not chemically or neurologically paralyzed, and free of other medical or surgical issues prohibiting extubation. Just before the extubation trial, all patients had been weaned to continuous positive airway pressure mode. Only those patients who met the criteria described earlier were considered for a 2-minute extubation protocol (TMEP). All patients received continuous electrocardiography, respiratory rate, and pulse oximetry saturation monitoring. Blood pressure monitoring was either continuous with an arterial line or intermittent with an automated noninvasive cuff.
The distributions of the continuous variables were examined for normality. Continuous variables showing positive skew were normalized by log transformation. Homogeneity of group variance was assessed by the folded F-test. Twogroup comparisons of continuous variables were made using the independent-samples t-test if both the normality and homogeneity of variance assumptions were satisfied. If there was evidence only against homogeneity of variance, the Satterthwaite adjustment was used. If the normalizing transformation failed or the outcome variable was ordinal, 2 group comparisons were made by the Wilcoxon rank-sum test. Categoric variables were compared using the Fisher exact test. Predictors of an event were assessed using logistic regression models. A P value of less than .05 was taken as the measure of statistical significance.
Results During the study period, 485 intubated patients were cared for in the SICU. Complete data were collected on 213 patients (106 men; 107 women). Table 1 shows the major diagnoses and procedures for these patients, including neurosurgery (21%), and trauma surgery and colon surgery (14% each). Ninety-five percent of this patient population had no comorbid pulmonary disease and most study patients
892 Table 1
The American Journal of Surgery, Vol 196, No 6, December 2008 Diagnosis/procedure
Table 3
Reason for intubation
Number of patients (%) Neurosurgery Trauma Colon surgery Hepatobiliary surgery Upper-gastrointestinal surgery Spine surgery Liver transplant Vascular surgery Gynecologic surgery Urologic surgery Other
44 30 30 20 18 15 10 8 7 7 24
(20.7) (14.1) (14.1) (9.4) (8.4) (7.0) (4.7) (3.8) (3.3) (3.3) (11.3)
underwent a surgical procedure (Table 2). Thus, the most common indications for intubation were continued postoperative ventilation (65%) and altered mental status (22%) (Table 3). A total of 15 of the 213 patients (7%) required reintubation during their ICU stay (Table 4). Ten patients required reintubation within 24 hours of extubation, for a failure rate of 4.7%. One patient required reintubation between 24 and 48 hours after extubation, and 4 patients were reintubated well beyond 48 hours, but during the same ICU stay (range, 54 –120 hours postextubation). The reason for reintubation was respiratory distress in 13 of the 15 patients (87%) and altered mental status in 2 patients (13%). The 198 patients who were extubated successfully were compared with the 15 patients who required reintubation (Table 5). No statistically significant difference was found between the 2 groups with regard to age, basal metabolic index, admission Apache II score/SAPS, as well as APACHE II score at extubation. However, patients requiring reintubation showed a higher SAPS on the day of extubation (P ⫽ .03), tripled ICU LOS (P ⬍ .0001), and nearly doubled hospital LOS (P ⫽ .001). Furthermore, patients who were reintubated had been intubated more then twice as long as those who were extubated successfully (P ⫽ .005). Reintubated patients had an approximately 20% lower pretrial tidal volume and a 15% higher posttrial respiratory rate, both of which were significantly different from patients who did not require reintubation (P ⬍ .0001 and P ⫽ .03, respectively). The overall hospital mortality rate for the patients in this study was 6% (12 of 213). One of the 12 patients who died
Table 2
Number of patients (%) Recovery from anesthesia Altered mental status Respiratory distress Cardiopulmonary arrest
139 (65.3) 46 (21.6) 26 (12.2) 2 (.9)
was in the reintubation group (Table 6). When comparing parameters such as sex, ventilator settings, amount of pulmonary secretions on the day of extubation, arterial blood gas, PaO2/fraction of inspired oxygen, pretrial and posttrial blood pressure, HR, RR, oxygen saturation, RR/tidal volume (TV), and minute ventilation no statistically significant difference was found between successfully extubated patients and those who required reintubation (data not shown).
Comments It often is difficult to ascertain precisely when to discontinue mechanical ventilation. In practice, the decision to extubate a patient must be balanced with the possibility of extubation failure, which can have grave consequences. Reintubation is associated with an 8-fold increased risk for nosocomial pneumonia and up to an 8-fold increased risk for death.14 –17 The TMEP presented in this study proved to be a safe and effective method to allow physicians to determine when patients could be extubated. Its short 2-minute duration did not subject patients to the potential risks and discomforts associated with prolonged trial periods required by other extubation protocols. It allows physicians to assess patients during rounds as part of the routine physical examination, or at any other time when patients meet criteria to enter an extubation trial. Furthermore, it is a noninvasive method that does not require specialized personnel or therapists to be in attendance. Finally, no additional tests are required to perform this evaluation, and thus no additional costs are incurred. In this study, the reintubation rate within 24 hours of TMEP-screened extubation was 4.7% and the overall TMEP reintubation rate for all patients requiring reintubation at any time during their ICU stay remained low at 7.0%. These are impressive results for a noninvasive, quick, and inexpensive screening test. The incidence of reintubation in
Pulmonary disease Number of patients (%)
None Chronic obstructive pulmonary disease Pulmonary contusion Hypoventilation Lung cancer
Table 4
201 (94.4) 8 2 1 1
(3.8) (.9) (.5) (.5)
⬍24 h ⬍48 h ⬎48 h
Reintubation rate Rate (number of patients)
95% confidence interval
4.7% (10) 5.2% (11) 1.9% (4)
2.3–8.5 2.6–9.1 .5–4.7
A.A. Nisim et al. Table 5
TMEP for ICU patients
893
Successful extubations versus reintubations Successfully extubated (n ⫽ 198)
SAPS at extubation ICU LOS, d Hospital LOS, d Intubation days Pretrial Glasgow Coma Score Pretrial TV, mL Posttrial RR, breaths/min Age, y Basal metabolic index APACHE II score at admission SAPS at admission APACHE II score at extubation
14.8 5.6 21.1 2.6 10.9 540 19.5 58.2 26.0 23.9 15.2 22.6
Reintubated (n ⫽ 15)
(14.0) ⫹ 2.1 (3.0) ⫹ 2.6 (16.0) ⫹ 4.2 (2.0) ⫹ 1.6 (11.0) ⫹ .7 (480) ⫹ 15 (19.5) ⫹ 2.4 (59.0) ⫹ 4.5 (24.7) ⫹ 2.7 (24.0) ⫹ 2.6 (15.0) ⫹ 2.2 (22.0) ⫹ 2.3
16.5 18.7 38.1 5.3 10.7 410 22.9 60.7 26.0 26.7 16.5 22.5
(17.0) ⫹ 1.6 (18.0) ⫹ 2.9 (29.0) ⫹ 5.2 (5.0) ⫹ 2.0 (11.0) ⫹ .7 (400) ⫹ 90 (24.0) ⫹ 2.5 (55.0) ⫹ 4.3 (24.7) ⫹ 2.4 (27.0) ⫹ 2.6 (16.0) ⫹ 1.9 (22.0) ⫹ 2.3
P .03* ⬍.0001* .001* .005* .02* ⬍.0001* .03* .643 .992 .124 .294 .935
Results were reported as mean (median) ⫹ SEM. *Statistically significant.
other studies is reported to be as high as 42%.9,18 –24 Leitch et al,18 using a clinical judgment-based approach to ventilator weaning and extubation in 163 consecutive patients, reported a reintubation rate of only 1.8%. Because of the low reintubation rates, the TMEP can be used safely and independently as a predictor of patients who potentially could be extubated. Patients who required reintubation had a higher SAPS, lower pretrial tidal volumes, higher posttrial respiratory rate on the day of extubation, and longer duration of intubation before extubation, so these factors could be considered in the decision to extubate. As expected, the most common causes of reintubation in our patient population were respiratory failure and altered mental status. Hospital costs are clearly reduced when patients are safely and expeditiously extubated. The reintubated patients incurred significantly longer ICU LOS and hospital LOS. Hospital costs and LOS are approximately 2.5 and 1.7 times greater, respectively, in mechanically ventilated ICU patients. This translates to an additional $1,500 in hospital costs for each additional ventilated day, and even more when ventilator-associated pneumonias or other complications supervene.5,25 These findings are similar to those reported by previous studies.26,27 The mortality rate in this study was 5.6% (12 of 213 patients). Only 1 of the patients who died required reintubation. This was a neurosurgical patient who underwent a
palliative tumor resection and subsequently suffered a massive hemorrhagic stroke requiring reintubation. Esteban et al16 found a much higher mortality rate in patients who required reintubation compared with those who did not (27.0% vs 2.6%; P ⬍ .001). Limitations of our study included a study population confined to surgical patients in a SICU. The TMEP method has not been studied in cardiothoracic or medical patients. As such, this study does not reflect the protocol’s ability to reliably predict extubation in those populations. However, its success highlights the need for new studies in these patients. In addition, because reintubation rates were low, it was difficult to assess the predictive nature of this protocol. To reliably do so, a much larger sample size is required. Finally, some intubated patients had incomplete data and thus were excluded.
Conclusions The TMEP is a simple, rapid, safe, noninvasive, inexpensive, and effective method of predicting successful extubation in SICU patients. TMEP can be used as a practical tool for daily evaluation of patients who potentially could be extubated, eliminating the need for more expensive or timeconsuming methods.
Acknowledgments Table 6
Discharge disposition Number of patients (%)
Home Rehabilitation Skilled nursing facility Death Other Acute care hospital
106 52 27 12 9 8
(49.7) (24.4) (12.7) (5.6) (4.1) (3.8)
The authors would like to thank James Mirocha for his statistical expertise and Jocelyn Ho, MD, and Jonathan Pryor, MD, for their assistance in data collection.
References 1. Rumbak MJ, Walsh FW, Anderson WM, et al. Significant tracheal obstruction causing failure to wean in patients requiring prolonged me-
894
2.
3.
4. 5.
6.
7.
8.
9.
10. 11.
12.
13.
14.
15. 16.
17.
18.
19.
20.
21.
22.
The American Journal of Surgery, Vol 196, No 6, December 2008
chanical ventilation: a forgotten complication of long-term mechanical ventilation. Chest 1999;115:1092–5. Estes RJ, Meduri GU. The pathogenesis of ventilator-associated pneumonia. I. Mechanisms of bacterial transcolonization and airway inoculation. Intensive Care Med 1995;21:365– 83. Wason R, Gupta P, Gogia AR. Bilateral adductor vocal cord paresis following endotracheal intubation for general anaesthesia. Anaesth Intensive Care 2004;32:417– 8. Morehead RS, Pinto SJ. Ventilator-associated pneumonia. Arch Intern Med 2000;160:1926 –36. Safdar N, Dezfulian C, Collard HR, et al. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 2005;33:2184 –93. Anuzueto A, Frutas-Vivar F, Esteban A, et al. Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients. Intensive Care Med 2004;30:612–9. MacIntyre NR. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine. Chest 2001;120:375–96. Kollef MH, Shapiro SD, Silver P, et al. A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit Care Med 1997;25:567–74. Yang K, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 1991;324:1445–50. Burns SM, Burns JE, Truwit JD. Comparison of five clinical weaning indices. Am J Crit Care 1994;3:342–52. Marini JJ, Smith TC, Lamb V. Estimation of inspiratory muscle strength in mechanically ventilated patients: the measurement of maximal inspiratory pressure. J Crit Care 1986;1:32– 8. Lee KH, Hui KP, Chan TB, et al. Rapid shallow breathing (frequencytidal volume ratio) did not predict extubation outcome. Chest 1994; 105:540 –3. Fernando FV, Furguson ND, Esteban A, et al. Risk factors for extubation failure in patients following a successful spontaneous breathing trial. Chest 2006;130:1664 –71. Torres A, Gatell JM, Aznar E, et al. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med 1995;152:137– 41. Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186 –92. Esteban A, Alia I, Gordo F, et al. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation; the Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1997;156:459 – 65. Esteban A, Alia I, Tobin MJ, et al. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation; the Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1999;159:512– 8. Leitch EA, Moran JL, Grealy B. Weaning and extubation in the intensive care unit. Clinical or index-driven approach? Intensive Care Med 1995;22:752–9. Broachard L, Rauss A, Benito S, et al. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med 1994;150:896 – 903. Esteban A, Frutos F, Tobin MJ, et al, for the Spanish Lung Failure Collaborative Group. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995;332:345–50. Demling RH, Read T, Lind LJ, et al. Incidence and morbidity of extubation failure in surgical intensive care patients. Crit Care Med 1988;16:573–77. Tahvanainen J, Salmenpera M, Nikki P. Extubation criteria after weaning from intermittent mandatory ventilatory and continuous positive airway pressure. Crit Care Med 1983;11:702–7.
23. Miller RL, Cole RP. Association between reduced cuff leak volume and postextubation strider. Chest 1996;110:1035– 40. 24. Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335:1864 –9. 25. Needham DM, Pronovost PJ. The importance of understanding the costs of critical care and mechanical ventilation. Crit Care Med 2005; 33:1266 –71. 26. Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186 –92. 27. Daley BJ, Gracia-Perez F, Ross SE. Reintubation as an outcome predictor in trauma patients. Chest 1996;110:1577– 80.
Discussion Dr. Ram Nirula (Salt Lake City, UT): Your concern is that the weaning parameters such as rapid shallow breathing index (RSBI) and NIF and the ventilation that we currently use frequently identify patients that will fail extubation, but they also fail to predict those who could potentially successfully extubate. You point out that the specificity of the commonly used RSBI is only 64% in one of several studies. The issue therefore that you are addressing is that the parameters that we currently use may keep many patients intubated longer than they may need to be. The fact that more than 95% of your patients remained extubated for more than 24 hours may simply reflect a selection based upon the ability to wean the minimal vent settings. Can you give us some information about how long these patients were on minimal vent settings before the 2-minute trial was employed? As you stated in your manuscript, patients that failed the 2-minute trial were placed back on the ventilator and you point out that the weaning parameters that we currently use have poor specificity. So, if all patients who failed the 2-minute trial were placed back on the ventilator, there is no way to capture those patients who might have been extubatable despite failing the 2-minute trial. Now, obviously, it is inhumane to take patients who fail the 2-minute trial and then extubate them, but based on the concerns that you raise about the existing literature having poor specificity, you cannot calculate specificity based on your trial design since there is no false positives. Your results indicate that patients who were reintubated had a significantly lower pretrial tidal volume and a higher posttrial extubation rate. Yet there was no statistically significant difference in RSBI between these 2 groups. You do not show that data in your manuscript. Can you explain the reason for the discrepancy in your findings and is this simply related to the fact that you had such a low reintubation rate, but there was no statistical significance? Lastly, are the respiratory therapists and residents now performing the 2-minute trial at 1 AM in the morning and extubating these patients at that time or do they wait until morning rounds under the watchful eyes of Dr. Margulies and Dr. Shabot? Dr. Abraham Avi Nisim (Los Angeles, CA): Thank you very much. As far as how long we wait before conducting the 2-minute trial, I think that is key to this particular test. First of all, we need to realize this test, especially due to its
A.A. Nisim et al.
TMEP for ICU patients
duration and the requirements to conduct this test, which are minimal as far as equipment and personnel, can be conducted at any time of the day. We typically have the patients on continuous positive airway pressure ventilation for several hours to make sure they are at low-pressure support, to make sure they are not in respiratory distress, make sure that they are able to mentate and cooperate before conducting the trial, so as far as how long, it does vary. We do see the patients regularly in the ICU and when we feel that they are hemodynamically and neurologically ready for an extubation trial, we go ahead and evaluate them. If for some reason they are not there just yet, we will wait and come back a couple of hours later, the nature of this being just a short test allows us that luxury to stop at any time and evaluate them. As far as false positives in this test, yes, the reintubation rates are very low in this study, which obviously limit our ability to talk about things like positive predictive values and negative predictive values. Of point, all the patients who were reintubated are patients who actually passed the 2-minute extubation trial and were extubated who later required reintubation. As far as looking at RSBI and NIF, in comparing its reliability compared to the 2-minute extuba-
895 tion, we are not here to say that things like RSBI and NIF are not good tools to utilize. We are saying that this particular test is a very short test which could be utilized in conjunction or, more importantly, independently. Yes, we are not able to obtain values concerning positive predictive values and sensitivities and specificities mostly because of the reintubation rates being so low, but in much larger studies these numbers can be extracted. As far as this test being 2 minutes versus 2 hours, I think that there is a great advantage to having a 2-minute test. We do watch these patients continuously in the ICU as I said earlier. It is much more comfortable for the patients obviously not to have them on a T-tube or to observe them for a 2-hour period of time to see how they do before considering extubation. As far as extubations at night, we have the surgical ICU staffed by residents all day long and all night long. We do conduct these tests in the morning and at night without the necessity for any additional personnel to do so. So we do extubate patients in the middle of the night and with the same kind of efficiency because again this particular method is protocolized and standardized, so if we follow all the steps, there is no difference.
The Southwestern Surgical Congress
A 2-minute pre-extubation protocol for ventilated intensive care unit patients Abraham Avi Nisim, M.D., Daniel R. Margulies, M.D.*, Matthew T. Wilson, M.D., Rodrigo F. Alban, M.D., Catherine M. Dang, M.D., Alexander D. Allins, M.D., M. Michael Shabot, M.D. Trauma Surgery and Surgical Critical Care, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Suite 8215, Los Angeles, CA 90048, USA KEYWORDS: Extubation; Reintubation; Ventilator weaning
Abstract BACKGROUND: Clinicians often are challenged with safely predicting the optimal time of extubation for ventilated patients. Commonly used weaning parameters have poor positive predictive value for successful extubation. METHODS: A total of 213 intubated patients in our 20-bed surgical intensive care unit were enrolled in a trial to test a prospective, observational, 2-minute extubation protocol (TMEP). Daily measurements were obtained on all intubated patients who met criteria, which included adequate oxygenation, systolic blood pressure, heart rate, hemoglobin, Glasgow Coma Score greater than 10t, absence of significant metabolic/respiratory acidosis, and absence of therapeutic or neurologic paralysis. During TMEP, endotracheally intubated patients were physically disconnected from the ventilator for a 2-minute period of observation while spontaneously breathing room air. Patients were extubated if they tolerated the trial without clinically significant desaturation or alteration of vital signs or mental status. RESULTS: The TMEP reliably predicted successful extubations in 203 of 213 patients (95.3%). Patients who required reintubation had a longer intensive care unit stay and a longer hospital stay. CONCLUSIONS: TMEP is a simple and reliable method of predicting successful extubation. © 2008 Elsevier Inc. All rights reserved.
Discontinuing mechanical ventilation has long been more of an art than a science. With the widespread use of positive-pressure mechanical ventilation via endotracheal tubes, numerous potential complications exist including ventilator-associated pneumonia, tracheal stenosis, vocal cord paresis, and ventilator-induced lung injury.1– 6 Consequently, one of the goals of modern intensive care unit
* Corresponding author: Tel.: ⫹1-310-423-5874; fax: ⫹1-310-4230139. E-mail address: [email protected] Manuscript received May 3, 2008; revised manuscript July 3, 2008
0002-9610/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2008.07.038
(ICU) management is to discontinue mechanical ventilation as quickly and safely as possible. Before the discontinuation of mechanical ventilation, all ventilatory and nonventilatory issues that necessitated mechanical ventilation should be corrected.7 These include gas exchange abnormalities, loss of central respiratory drive as a result of stroke or metabolic derangement, and ventilatory muscle fatigue as a result of mismatched ventilatory demand. To determine when ventilator weaning should be initiated, objective measurements such as adequate oxygenation (PaO2 ⱖ 60 mm Hg on a fraction of inspired oxygen ⱕ 40%, positive end-expiratory pressure ⱕ 8 cm H2O), systolic blood pressure greater than 90 mm Hg, heart rate (HR)
A.A. Nisim et al.
TMEP for ICU patients
greater than 60 bpm, absence of significant metabolic/respiratory acidosis (pH ⱖ 7.25), adequate hemoglobin level (8 –10 g/dL), and adequate mentation (Glasgow Coma Score ⱖ 13), and spontaneous breathing also should be confirmed.7 In a randomized controlled trial, Kollef et al8 showed that traditional physician-directed discontinuation of mechanical ventilation is associated with increased duration of mechanical ventilation and cost when compared with protocol-directed ventilator weaning. Therefore, a simple, reproducible, highly specific, and sensitive test for discontinuing mechanical ventilation is needed. The commonly used weaning parameters have not been proven to definitively predict extubation outcome. In a prospective study of 64 patients, minute ventilation greater than 10 L failed to predict successful extubation in 40% of patients.9 Likewise, negative inspiratory force (NIF) and maximal inspiratory pressure greater than ⫺20 cm H2O have poor positive predictive value, although they appear to have greater utility in predicting unsuccessful discontinuation of ventilatory support.9 –11 Even the rapid shallow breathing index (respiratory rate/tidal volume ratio, ⬍105 /L) has a specificity of only 64%.9,12,13 Consequently, we sought to identify a simple bedside method to predict extubation outcome. We hypothesized that successful completion of a 2-minute spontaneous breathing trial on room air off the ventilator would predict successful discontinuation of mechanical ventilation.
891 The TMEP was performed by physically disconnecting the patient from the ventilator while remaining endotracheally intubated for a 2-minute period of observation. During that time, the patient spontaneously breathed room air and was monitored continuously for distress or changes in hemodynamics or ventilatory status. The decision to extubate were made either as part of morning rounds by the ICU team, which included attendings, fellows, and surgical residents, or at any time when the patients met criteria for an extubation trial by any individual on the ICU team at bedside. Evaluating physicians remained at the bedside observing the patient throughout the trial. At the end of the 2-minute trial (or earlier if the patient became unstable) the patient was reconnected to the ventilator. Patients were extubated if they tolerated the trial without distress, with hemodynamic and respiratory stability, respiratory rate of less than 30, and saturation greater than 90%. Data collection included patient demographics, diagnosis, pulmonary disease, Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS), basal metabolic index, total ICU length of stay (LOS), and hospital LOS. Pre-TMEP and end-of-trial blood pressure, HR, RR, and percentage of saturation were recorded. A pretrial arterial blood gas also was obtained. A successful trial was defined as any patient who did not require reintubation within 24 hours of extubation.
Statistical analysis
Patients and Methods This prospective observational study was conducted in an urban 951-bed Level I trauma and multi-organ transplant center. Intubated patients cared for in a 20-bed surgical ICU (SICU) from January 1 to December 31, 2005, were included. Patients undergoing cardiac and thoracic procedures were cared for in a different ICU and were not included in this study. The population was a convenience sample of patients with complete data. The study protocol was approved by the Institutional Review Board at Cedars-Sinai Medical Center. Daily physiologic measurements were obtained on all intubated patients who were hemodynamically stable (systolic blood pressure ⬎ 90 mm Hg, 10 ⬍ respiratory rate [RR] ⬍ 30, 60 ⬍ HR ⬍ 110 bpm), GCS greater than 10 t (intubated), not chemically or neurologically paralyzed, and free of other medical or surgical issues prohibiting extubation. Just before the extubation trial, all patients had been weaned to continuous positive airway pressure mode. Only those patients who met the criteria described earlier were considered for a 2-minute extubation protocol (TMEP). All patients received continuous electrocardiography, respiratory rate, and pulse oximetry saturation monitoring. Blood pressure monitoring was either continuous with an arterial line or intermittent with an automated noninvasive cuff.
The distributions of the continuous variables were examined for normality. Continuous variables showing positive skew were normalized by log transformation. Homogeneity of group variance was assessed by the folded F-test. Twogroup comparisons of continuous variables were made using the independent-samples t-test if both the normality and homogeneity of variance assumptions were satisfied. If there was evidence only against homogeneity of variance, the Satterthwaite adjustment was used. If the normalizing transformation failed or the outcome variable was ordinal, 2 group comparisons were made by the Wilcoxon rank-sum test. Categoric variables were compared using the Fisher exact test. Predictors of an event were assessed using logistic regression models. A P value of less than .05 was taken as the measure of statistical significance.
Results During the study period, 485 intubated patients were cared for in the SICU. Complete data were collected on 213 patients (106 men; 107 women). Table 1 shows the major diagnoses and procedures for these patients, including neurosurgery (21%), and trauma surgery and colon surgery (14% each). Ninety-five percent of this patient population had no comorbid pulmonary disease and most study patients
892 Table 1
The American Journal of Surgery, Vol 196, No 6, December 2008 Diagnosis/procedure
Table 3
Reason for intubation
Number of patients (%) Neurosurgery Trauma Colon surgery Hepatobiliary surgery Upper-gastrointestinal surgery Spine surgery Liver transplant Vascular surgery Gynecologic surgery Urologic surgery Other
44 30 30 20 18 15 10 8 7 7 24
(20.7) (14.1) (14.1) (9.4) (8.4) (7.0) (4.7) (3.8) (3.3) (3.3) (11.3)
underwent a surgical procedure (Table 2). Thus, the most common indications for intubation were continued postoperative ventilation (65%) and altered mental status (22%) (Table 3). A total of 15 of the 213 patients (7%) required reintubation during their ICU stay (Table 4). Ten patients required reintubation within 24 hours of extubation, for a failure rate of 4.7%. One patient required reintubation between 24 and 48 hours after extubation, and 4 patients were reintubated well beyond 48 hours, but during the same ICU stay (range, 54 –120 hours postextubation). The reason for reintubation was respiratory distress in 13 of the 15 patients (87%) and altered mental status in 2 patients (13%). The 198 patients who were extubated successfully were compared with the 15 patients who required reintubation (Table 5). No statistically significant difference was found between the 2 groups with regard to age, basal metabolic index, admission Apache II score/SAPS, as well as APACHE II score at extubation. However, patients requiring reintubation showed a higher SAPS on the day of extubation (P ⫽ .03), tripled ICU LOS (P ⬍ .0001), and nearly doubled hospital LOS (P ⫽ .001). Furthermore, patients who were reintubated had been intubated more then twice as long as those who were extubated successfully (P ⫽ .005). Reintubated patients had an approximately 20% lower pretrial tidal volume and a 15% higher posttrial respiratory rate, both of which were significantly different from patients who did not require reintubation (P ⬍ .0001 and P ⫽ .03, respectively). The overall hospital mortality rate for the patients in this study was 6% (12 of 213). One of the 12 patients who died
Table 2
Number of patients (%) Recovery from anesthesia Altered mental status Respiratory distress Cardiopulmonary arrest
139 (65.3) 46 (21.6) 26 (12.2) 2 (.9)
was in the reintubation group (Table 6). When comparing parameters such as sex, ventilator settings, amount of pulmonary secretions on the day of extubation, arterial blood gas, PaO2/fraction of inspired oxygen, pretrial and posttrial blood pressure, HR, RR, oxygen saturation, RR/tidal volume (TV), and minute ventilation no statistically significant difference was found between successfully extubated patients and those who required reintubation (data not shown).
Comments It often is difficult to ascertain precisely when to discontinue mechanical ventilation. In practice, the decision to extubate a patient must be balanced with the possibility of extubation failure, which can have grave consequences. Reintubation is associated with an 8-fold increased risk for nosocomial pneumonia and up to an 8-fold increased risk for death.14 –17 The TMEP presented in this study proved to be a safe and effective method to allow physicians to determine when patients could be extubated. Its short 2-minute duration did not subject patients to the potential risks and discomforts associated with prolonged trial periods required by other extubation protocols. It allows physicians to assess patients during rounds as part of the routine physical examination, or at any other time when patients meet criteria to enter an extubation trial. Furthermore, it is a noninvasive method that does not require specialized personnel or therapists to be in attendance. Finally, no additional tests are required to perform this evaluation, and thus no additional costs are incurred. In this study, the reintubation rate within 24 hours of TMEP-screened extubation was 4.7% and the overall TMEP reintubation rate for all patients requiring reintubation at any time during their ICU stay remained low at 7.0%. These are impressive results for a noninvasive, quick, and inexpensive screening test. The incidence of reintubation in
Pulmonary disease Number of patients (%)
None Chronic obstructive pulmonary disease Pulmonary contusion Hypoventilation Lung cancer
Table 4
201 (94.4) 8 2 1 1
(3.8) (.9) (.5) (.5)
⬍24 h ⬍48 h ⬎48 h
Reintubation rate Rate (number of patients)
95% confidence interval
4.7% (10) 5.2% (11) 1.9% (4)
2.3–8.5 2.6–9.1 .5–4.7
A.A. Nisim et al. Table 5
TMEP for ICU patients
893
Successful extubations versus reintubations Successfully extubated (n ⫽ 198)
SAPS at extubation ICU LOS, d Hospital LOS, d Intubation days Pretrial Glasgow Coma Score Pretrial TV, mL Posttrial RR, breaths/min Age, y Basal metabolic index APACHE II score at admission SAPS at admission APACHE II score at extubation
14.8 5.6 21.1 2.6 10.9 540 19.5 58.2 26.0 23.9 15.2 22.6
Reintubated (n ⫽ 15)
(14.0) ⫹ 2.1 (3.0) ⫹ 2.6 (16.0) ⫹ 4.2 (2.0) ⫹ 1.6 (11.0) ⫹ .7 (480) ⫹ 15 (19.5) ⫹ 2.4 (59.0) ⫹ 4.5 (24.7) ⫹ 2.7 (24.0) ⫹ 2.6 (15.0) ⫹ 2.2 (22.0) ⫹ 2.3
16.5 18.7 38.1 5.3 10.7 410 22.9 60.7 26.0 26.7 16.5 22.5
(17.0) ⫹ 1.6 (18.0) ⫹ 2.9 (29.0) ⫹ 5.2 (5.0) ⫹ 2.0 (11.0) ⫹ .7 (400) ⫹ 90 (24.0) ⫹ 2.5 (55.0) ⫹ 4.3 (24.7) ⫹ 2.4 (27.0) ⫹ 2.6 (16.0) ⫹ 1.9 (22.0) ⫹ 2.3
P .03* ⬍.0001* .001* .005* .02* ⬍.0001* .03* .643 .992 .124 .294 .935
Results were reported as mean (median) ⫹ SEM. *Statistically significant.
other studies is reported to be as high as 42%.9,18 –24 Leitch et al,18 using a clinical judgment-based approach to ventilator weaning and extubation in 163 consecutive patients, reported a reintubation rate of only 1.8%. Because of the low reintubation rates, the TMEP can be used safely and independently as a predictor of patients who potentially could be extubated. Patients who required reintubation had a higher SAPS, lower pretrial tidal volumes, higher posttrial respiratory rate on the day of extubation, and longer duration of intubation before extubation, so these factors could be considered in the decision to extubate. As expected, the most common causes of reintubation in our patient population were respiratory failure and altered mental status. Hospital costs are clearly reduced when patients are safely and expeditiously extubated. The reintubated patients incurred significantly longer ICU LOS and hospital LOS. Hospital costs and LOS are approximately 2.5 and 1.7 times greater, respectively, in mechanically ventilated ICU patients. This translates to an additional $1,500 in hospital costs for each additional ventilated day, and even more when ventilator-associated pneumonias or other complications supervene.5,25 These findings are similar to those reported by previous studies.26,27 The mortality rate in this study was 5.6% (12 of 213 patients). Only 1 of the patients who died required reintubation. This was a neurosurgical patient who underwent a
palliative tumor resection and subsequently suffered a massive hemorrhagic stroke requiring reintubation. Esteban et al16 found a much higher mortality rate in patients who required reintubation compared with those who did not (27.0% vs 2.6%; P ⬍ .001). Limitations of our study included a study population confined to surgical patients in a SICU. The TMEP method has not been studied in cardiothoracic or medical patients. As such, this study does not reflect the protocol’s ability to reliably predict extubation in those populations. However, its success highlights the need for new studies in these patients. In addition, because reintubation rates were low, it was difficult to assess the predictive nature of this protocol. To reliably do so, a much larger sample size is required. Finally, some intubated patients had incomplete data and thus were excluded.
Conclusions The TMEP is a simple, rapid, safe, noninvasive, inexpensive, and effective method of predicting successful extubation in SICU patients. TMEP can be used as a practical tool for daily evaluation of patients who potentially could be extubated, eliminating the need for more expensive or timeconsuming methods.
Acknowledgments Table 6
Discharge disposition Number of patients (%)
Home Rehabilitation Skilled nursing facility Death Other Acute care hospital
106 52 27 12 9 8
(49.7) (24.4) (12.7) (5.6) (4.1) (3.8)
The authors would like to thank James Mirocha for his statistical expertise and Jocelyn Ho, MD, and Jonathan Pryor, MD, for their assistance in data collection.
References 1. Rumbak MJ, Walsh FW, Anderson WM, et al. Significant tracheal obstruction causing failure to wean in patients requiring prolonged me-
894
2.
3.
4. 5.
6.
7.
8.
9.
10. 11.
12.
13.
14.
15. 16.
17.
18.
19.
20.
21.
22.
The American Journal of Surgery, Vol 196, No 6, December 2008
chanical ventilation: a forgotten complication of long-term mechanical ventilation. Chest 1999;115:1092–5. Estes RJ, Meduri GU. The pathogenesis of ventilator-associated pneumonia. I. Mechanisms of bacterial transcolonization and airway inoculation. Intensive Care Med 1995;21:365– 83. Wason R, Gupta P, Gogia AR. Bilateral adductor vocal cord paresis following endotracheal intubation for general anaesthesia. Anaesth Intensive Care 2004;32:417– 8. Morehead RS, Pinto SJ. Ventilator-associated pneumonia. Arch Intern Med 2000;160:1926 –36. Safdar N, Dezfulian C, Collard HR, et al. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 2005;33:2184 –93. Anuzueto A, Frutas-Vivar F, Esteban A, et al. Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients. Intensive Care Med 2004;30:612–9. MacIntyre NR. Evidence-based guidelines for weaning and discontinuing ventilatory support: a collective task force facilitated by the American College of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine. Chest 2001;120:375–96. Kollef MH, Shapiro SD, Silver P, et al. A randomized, controlled trial of protocol-directed versus physician-directed weaning from mechanical ventilation. Crit Care Med 1997;25:567–74. Yang K, Tobin MJ. A prospective study of indexes predicting the outcome of trials of weaning from mechanical ventilation. N Engl J Med 1991;324:1445–50. Burns SM, Burns JE, Truwit JD. Comparison of five clinical weaning indices. Am J Crit Care 1994;3:342–52. Marini JJ, Smith TC, Lamb V. Estimation of inspiratory muscle strength in mechanically ventilated patients: the measurement of maximal inspiratory pressure. J Crit Care 1986;1:32– 8. Lee KH, Hui KP, Chan TB, et al. Rapid shallow breathing (frequencytidal volume ratio) did not predict extubation outcome. Chest 1994; 105:540 –3. Fernando FV, Furguson ND, Esteban A, et al. Risk factors for extubation failure in patients following a successful spontaneous breathing trial. Chest 2006;130:1664 –71. Torres A, Gatell JM, Aznar E, et al. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med 1995;152:137– 41. Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186 –92. Esteban A, Alia I, Gordo F, et al. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation; the Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1997;156:459 – 65. Esteban A, Alia I, Tobin MJ, et al. Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation; the Spanish Lung Failure Collaborative Group. Am J Respir Crit Care Med 1999;159:512– 8. Leitch EA, Moran JL, Grealy B. Weaning and extubation in the intensive care unit. Clinical or index-driven approach? Intensive Care Med 1995;22:752–9. Broachard L, Rauss A, Benito S, et al. Comparison of three methods of gradual withdrawal from ventilatory support during weaning from mechanical ventilation. Am J Respir Crit Care Med 1994;150:896 – 903. Esteban A, Frutos F, Tobin MJ, et al, for the Spanish Lung Failure Collaborative Group. A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995;332:345–50. Demling RH, Read T, Lind LJ, et al. Incidence and morbidity of extubation failure in surgical intensive care patients. Crit Care Med 1988;16:573–77. Tahvanainen J, Salmenpera M, Nikki P. Extubation criteria after weaning from intermittent mandatory ventilatory and continuous positive airway pressure. Crit Care Med 1983;11:702–7.
23. Miller RL, Cole RP. Association between reduced cuff leak volume and postextubation strider. Chest 1996;110:1035– 40. 24. Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996;335:1864 –9. 25. Needham DM, Pronovost PJ. The importance of understanding the costs of critical care and mechanical ventilation. Crit Care Med 2005; 33:1266 –71. 26. Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186 –92. 27. Daley BJ, Gracia-Perez F, Ross SE. Reintubation as an outcome predictor in trauma patients. Chest 1996;110:1577– 80.
Discussion Dr. Ram Nirula (Salt Lake City, UT): Your concern is that the weaning parameters such as rapid shallow breathing index (RSBI) and NIF and the ventilation that we currently use frequently identify patients that will fail extubation, but they also fail to predict those who could potentially successfully extubate. You point out that the specificity of the commonly used RSBI is only 64% in one of several studies. The issue therefore that you are addressing is that the parameters that we currently use may keep many patients intubated longer than they may need to be. The fact that more than 95% of your patients remained extubated for more than 24 hours may simply reflect a selection based upon the ability to wean the minimal vent settings. Can you give us some information about how long these patients were on minimal vent settings before the 2-minute trial was employed? As you stated in your manuscript, patients that failed the 2-minute trial were placed back on the ventilator and you point out that the weaning parameters that we currently use have poor specificity. So, if all patients who failed the 2-minute trial were placed back on the ventilator, there is no way to capture those patients who might have been extubatable despite failing the 2-minute trial. Now, obviously, it is inhumane to take patients who fail the 2-minute trial and then extubate them, but based on the concerns that you raise about the existing literature having poor specificity, you cannot calculate specificity based on your trial design since there is no false positives. Your results indicate that patients who were reintubated had a significantly lower pretrial tidal volume and a higher posttrial extubation rate. Yet there was no statistically significant difference in RSBI between these 2 groups. You do not show that data in your manuscript. Can you explain the reason for the discrepancy in your findings and is this simply related to the fact that you had such a low reintubation rate, but there was no statistical significance? Lastly, are the respiratory therapists and residents now performing the 2-minute trial at 1 AM in the morning and extubating these patients at that time or do they wait until morning rounds under the watchful eyes of Dr. Margulies and Dr. Shabot? Dr. Abraham Avi Nisim (Los Angeles, CA): Thank you very much. As far as how long we wait before conducting the 2-minute trial, I think that is key to this particular test. First of all, we need to realize this test, especially due to its
A.A. Nisim et al.
TMEP for ICU patients
duration and the requirements to conduct this test, which are minimal as far as equipment and personnel, can be conducted at any time of the day. We typically have the patients on continuous positive airway pressure ventilation for several hours to make sure they are at low-pressure support, to make sure they are not in respiratory distress, make sure that they are able to mentate and cooperate before conducting the trial, so as far as how long, it does vary. We do see the patients regularly in the ICU and when we feel that they are hemodynamically and neurologically ready for an extubation trial, we go ahead and evaluate them. If for some reason they are not there just yet, we will wait and come back a couple of hours later, the nature of this being just a short test allows us that luxury to stop at any time and evaluate them. As far as false positives in this test, yes, the reintubation rates are very low in this study, which obviously limit our ability to talk about things like positive predictive values and negative predictive values. Of point, all the patients who were reintubated are patients who actually passed the 2-minute extubation trial and were extubated who later required reintubation. As far as looking at RSBI and NIF, in comparing its reliability compared to the 2-minute extuba-
895 tion, we are not here to say that things like RSBI and NIF are not good tools to utilize. We are saying that this particular test is a very short test which could be utilized in conjunction or, more importantly, independently. Yes, we are not able to obtain values concerning positive predictive values and sensitivities and specificities mostly because of the reintubation rates being so low, but in much larger studies these numbers can be extracted. As far as this test being 2 minutes versus 2 hours, I think that there is a great advantage to having a 2-minute test. We do watch these patients continuously in the ICU as I said earlier. It is much more comfortable for the patients obviously not to have them on a T-tube or to observe them for a 2-hour period of time to see how they do before considering extubation. As far as extubations at night, we have the surgical ICU staffed by residents all day long and all night long. We do conduct these tests in the morning and at night without the necessity for any additional personnel to do so. So we do extubate patients in the middle of the night and with the same kind of efficiency because again this particular method is protocolized and standardized, so if we follow all the steps, there is no difference.