- Email: [email protected]
Preoperative hemoglobin concentration as an independent predictor for outcome after coronary artery bypass grafting
Accepted Manuscript Preoperative Hemoglobin concentration as an independent predictor for outcome after Coronary Artery Bypass Grafting Ammar Eltigani, Ayman Abdelaziz, Ali Kindawy, Hesham Ewila, Amr Badr, Ahmed Elmahrouk PII:
S1110-578X(16)30106-7
DOI:
10.1016/j.jescts.2016.11.004
Reference:
JESCTS 44
To appear in:
Journal of the Egyptian Society of Cardio-Thoracic Surgery
Received Date: 16 October 2016 Accepted Date: 10 November 2016
Please cite this article as: Eltigani A, Abdelaziz A, Kindawy A, Ewila H, Badr A, Elmahrouk A, Preoperative Hemoglobin concentration as an independent predictor for outcome after Coronary Artery Bypass Grafting, Journal of the Egyptian Society of Cardio-Thoracic Surgery (2017), doi: 10.1016/ j.jescts.2016.11.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Author group and affiliations Corresponding author: Ahmed Elmahrouk |CARDIOTHORACIC SURGERY DEPARTMENT TANTA UNIVERSITY, Egypt.
AC C
EP
TE D
M AN U
SC
RI PT
Ammar Eltigani (Hamad Medical Corporation), Ayman Abdelaziz (Hamad Medical Corporation), Ali Kindawy (Hamad Medical Corporation), Hesham Ewila (Department of Anesthesia, Suez Canal University, Egypt.), Amr Badr (Cardiology Department, Faculty of Medicine Tanta University)
ACCEPTED MANUSCRIPT
Preoperative Hemoglobin concentration as an independent predictor for outcome after Coronary Artery Bypass Grafting
RI PT
Hesham Ahmed Ewila,* Ammar Eltigani,** Ahmed Elmahrouk,***Ayman Abdelaziz,**** Ali Kindawi**
EP
TE D
M AN U
SC
Introduction: Preoperative anemia is accused for increased complications, morbidity and mortality following cardiac surgery. Due to the nature of cardiac patients who usually have poor myocardium reserve and multiple concomitant comorbidities, it is difficult to identify the role of preoperative hemoglobin concentration in the postoperative outcome. Accordingly, correction of low hemoglobin level prior to cardiac surgery still is a matter of debate. Aim of the work: To determine the impact of preoperative hemoglobin concentration on postoperative outcome following coronary artery bypass grafting. Methods: Data were collected on all patients who underwent coronary artery bypass grafting surgery in our hospital in the last three years. Preoperative Anemia was defined as hemoglobin level below 12 gm. /dl. Accordingly, three groups were identified: low, normal and high preoperative hemoglobin. Postoperative bleeding, red blood cells transfused, myocardial injury, infection rate, lengths of ventilation, renal injury and length of stay in intensive care unit were recorded. Results: We recruited 804 patients in our study. Preoperative anemia were identified in 159 patients assigned in group I. Patients in this group had postoperative blood transfusion in 69% of patients and postoperative bleeding > One liter in 31.6% of patients with P-value of 0.006,0.096 respectively. It showed higher postoperative infection rate in 9.5% of patients (P-value 0.49) and higher length of stay in ICU in 43.3% of patients (P value 0.003). Group II were 481 patients, whom had HB (12.1 -15 gm./dl) showed the shortest postoperative hospital stay in 56.1 % of patients, P value 0.0001. Group III, 164 patients had HB more than 15.1 gm. /dl. No cases of ICU readmission were recorded. Conclusion: -Preoperative hemoglobin level can be used as an indicator of outcome after cardiac surgery. Preoperative anemia should be optimized before coronary artery bypass grafting.
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
Key Words: CABG; Anemia; Predictor of Outcome
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
Introduction: Association between preoperative anemia and increased post-surgical complications has been established in patients undergoing non-cardiac surgery. Such increased risk is attributed to the effect of transfusions and the interactions between the co-morbidities and low hemoglobin levels. Preoperative anemia is a clinically important and increasingly frequent finding in patients presenting for cardiac surgery. In many of these patients, the perioperative risks are inherently high because of multiple concomitant diseases and are particularly aggravated when severe coronary artery disease is present.1–4 According to the World Health Organization (WHO), anemia is defined as hemoglobin level under 12 mg/dl in women and 13 mg/dl in men. 5 Because of their extremely limited coronary reserve, patients undergoing coronary artery bypass grafting (CABG) surgery represent a population potentially most sensitive to the impact of low hemoglobin levels.2,3,6,7 A significant association of anemia with increased perioperative morbidity and mortality has been questioned in a multitude of settings in cardiac surgery.1–8 Anemic patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) have higher morbidity ,mortality, perioperative acute myocardial infarction (AMI) and adverse event rates. 914 However, available data do not describe in details the exact relationship between the percentage of preoperative hemoglobin and the outcomes of CABG patients. In addition, it is unknown whether low hemoglobin levels cause the effects of anemia on outcome per se or by association with other risk factors frequently prevalent in anemic patients.4 Aim of the study: To review the impact of preoperative hemoglobin concentration on postoperative outcome and hemoglobin level as an independent predictor for morbidity and mortality. Methods: We performed a retrospective, descriptive, single-center study with purposive sampling that examined the occurrence of multiple complications after cardiac surgery. Approval for the study was obtained from the ethical committee (reference number 14498/14). After institutional research ethics board approval was obtained, data were retrospectively collected on consecutive adult (>18 years of age) patients who underwent CABG with cardiopulmonary bypass (CPB) from 2011-2014 in Qatar heart hospital, Hamad Medical Corporation. Patients were identified from hospital administrative databases in reverse chronological order starting from January 2014. We collected detailed perioperative,
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
operative and postoperative data (including demographics, laboratory tests, blood product transfusions, cross-clamp time, cardiopulmonary bypass time, postoperative drainage, re-exploration rates, wound infection, postoperative complications, and lengths of stay in the intensive care unit and hospital from existing clinical databases and hospital charts. Data were entered into a computerized database, which was programmed to accept only matching double-entry data falling within pre-specified ranges. All queries were resolved by referring to the patients’ original records. The cohort was distributed according to the preoperative Hemoglobin concentration and divided into three groups: Group I: 159 patients with low preoperative hemoglobin group: HB <12 g/dl. Group II: 481 patients with normal preoperative hemoglobin group: HB 12.1-15 g/dl Group III high: 164 patients with preoperative hemoglobin group: HB > 15 g/dl Exclusion Criteria: Patients who required emergency surgery were excluded from the study. Emergency surgery is always a high-risk procedure and would introduce difficult-to-control variables into the study. Patients who were dialysisdependent were excluded from analyses because chronic kidney disease alters hemoglobin, and anemia in these patients is most likely to be a marker for severity of illness. Similarly, we also excluded patients with impaired myocardial function (EF < 30%). Also excluded were patients with any clinically important bleeding in the last 6 months, recent blood transfusion (less than 2 weeks). If a patient underwent >1 relevant procedure during the study period, only the initial surgery was included for analysis. Dependent Variable: Taking anesthetic induction as the starting time, all clinically relevant outcomes were recorded: Postoperative bleeding, Number of red blood cells units transfused postoperatively, Prolongation of stay in the ICU or the hospital, Surgical wound infection, Acute kidney injury (>2-fold increase in creatinine concentration to above normal levels of 100 µmol/L in women and 110 µmol/L in men or the need for dialysis support). Cerebrovascular events, (any persistent new neurological deficit after surgery) Arrhythmias that includes atrial fibrillation (AF), ventricular tachycardia or ventricular fibrillation. Perioperative myocardial infarction, and use of inotropes (over 24 hours) postoperatively. Death from any cause during hospitalization was also recorded. Results:
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
TE D
M AN U
SC
RI PT
Clinical variables in the groups: We recruited eight hundred and four patients in our study. Patients were divided into three groups according to their preoperative HB concentration. Demographic data showed no significant difference between studied groups. Most of patients were males of non-Qatari ethnicity (table 1). Most of patients included have good preoperative left ventricular function. HBA1c level was higher in low HB level group. Most of patients in all groups underwent the operation with normal creatinine ratio with mild increase in preoperative creatinine level in low HB group. Data showed increase in bypass time in low preoperative HB group (table 1). Postoperative outcomes: Patients in group 1 had postoperative blood transfusion in 69% of patients and postoperative bleeding of more than one liter in 31.6% of patients with P-value of 0.006, 0.096 respectively (table 2). They showed higher postoperative infection rate in 9.5% of patients (P-value 0.49) and higher length of stay in ICU in 43.3% of patients (P value 0.003) (table 3). Group II were showed the shortest postoperative hospital stay in 56.1 % of patients, P value 0.0001. Group III, no cases of ICU readmission were recorded. No difference in respiratory complications between all groups. Three patients in-group 1 showed postoperative renal failure. Two patient proceeded for regular dialysis. No cases of acute postoperative myocardial infarction were recorded in all groups (table 3).
EP
Discussion: Anemia is a clinically important and increasingly frequent preoperative findings. It represents 20 % of patient admitted for cardiac surgery in our hospital. It has been related to increased postoperative complications and mortality. Nappi J (1) emphasized that anemia presence worsens outcomes after cardiac surgery whatever it is a result of a preexisting condition or surgical blood loss. Also Carson JL (2) et al concluded that anemia or intra operative blood loss increases the risk of death or postoperative complications in patients with cardiovascular disease than in those without. Relationship between anemia and postoperative complications after cardiac surgery had been demonestrated, (9,10) as studies failed to establish whether the occurrence of postoperative complications is due to low preoperative hemoglobin level per se or due to confounding effect of transfusions and the interactions between the co-morbidities. More studies are needed as recommended by karkouti et al (9). to investigate either treating preoperative anemia would improve the outcomes of patients undergoing cardiac
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
surgery. Our study was designed to investigate whether preoperative hemoglobin Concentration can be used as independent predictor of mortality and morbidity following coronary artery bypass grafting. We recruited 159 out of 803 patients who had preoperative anemia as hemoglobin level was below 12 gm/dl according to WHO definitions. Ferraris et al (6) suggest that older patients with preoperative anemia are at increased risk for postoperative complications, which was not clear in our study. As the mean age in the preoperative anemic patients group was 58 years. There were no significant differences between patient age in this group and ages in normal and high preoperative hemoglobin groups. Numerous preoperative risk factors may raise the propensity of postoperative complications in patients undergoing cardiac surgery: Poor cardiac functions, presence of diabetes mellitus, presence of hypertension and poor preoperative renal function. The extent of preexisting comorbidities substantially affects perioperative anemia tolerance Kulier A. (12) In our study, all patients were ASA physical status III–IV and Euro score, which we use to identify risks for morbidity and mortality, found to be matched in all groups. There are significant independent adverse effects of CPB hemodilutional anemia and intraoperative red blood cells transfusions on postoperative outcomes. In our study the 48.5 % of patients in the preoperative anemia group had prolonged bypass time more than 120 minutes but there were no significant differences when comparing to other groups. Regarding to postoperative outcome, Preoperative anemia is independently associated with adverse outcomes after cardiac surgery karkouti et al (9). which was clear in our study as patients in low preoperative hemoglobin group showed high incidence of postoperative blood transfusion in 69% of patients and it was statistically significant “P value 0.096” when comparing with patients in normal or high preoperative hemoglobin. Postoperative bleeding also was higher in this group as 31.6 % of patients bled more than one liter in the first 24 hours. Patients with low preoperative hemoglobin showed higher postoperative infection rate in 9.5% of patients (P-value 0.49) in comparison to other groups. Three patients in this group showed postoperative renal failure while two of them proceeded for regular dialysis. No cases of acute postoperative renal failure reported in the other groups. As postoperative anemia may play a role in postoperative myocardial ischemia and cardiac morbidity Nelson AH et al (17).
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
surprisingly we did not record any cases of acute postoperative myocardial ischemia or infarction was recorded in all groups. Patients with preoperative anemia recorded the higher length of stay in ICU in 43.3% of patients (P value 0.003) when compared to other groups while patients with normal preoperative hemoglobin had the shortest postoperative hospital stay as 56.1 % of patients, (P value 0.0001) discharged from the hospital less than one week postoperatively. Patients with high preoperative hemoglobin group (Hb > 15 gm/dl) did not record any intensive care readmission while in preoperative anemia group 5% of patients readmitted back to ICU. Zindrou et al (3) noted that low preoperative hemoglobin concentration of had a five-fold higher in-hospital mortality rate after surgery than those with a higher hemoglobin concentration, Which was coincided with our results as patients with low preoperative HB group had the higher mortality rate in 7.5% of patients while mortality rate was 3.5% in normal preoperative Hb group and 1.8 % of patients in high preoperative Hb group. So from our experience in Qatar heart hospital we can emphasize that preoperative hemoglobin concentration can be used as independent predictor of postoperative outcome following coronary artery bypass grafting. Optimization of preoperative hemoglobin is recommended to alleviate the burden of confounding preoperative risk factors and decrease postoperative adverse events Conclusion: The results of our study confirmed that preoperative hemoglobin level can be utilized as an independent predictor of morbidity and mortality following cardiac surgery. Therefore, we recommend that preoperative hemoglobin should be optimized prior to surgery whenever it is possible. Study strength and limitations References: 1. Nappi J. Anemia in patients with coronary artery disease. Am J Health Syst Pharm. 2003; 60: S4–S8. 2. Carson JL, Duff A, Poses RM, Berlin JA, Spence RK, Trout R, Noveck H, Strom BL. Effect of anemia and cardiovascular disease on surgical mortality and morbidity. Lancet. 1996; 348: 1055–1060. 3. Zindrou D, Taylor KM, Bagger JP. Preoperative hemoglobin concentration and mortality rate after coronary artery bypass surgery. Lancet. 2002; 359: 1747– 1748. 4. G. lobel, M. Javidroozi, A.Shander: Risk of Anemia in cardiac Surgery
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
CARDIOTHORAC
VASC
ANESTH
December
TE D
M AN U
SC
RI PT
5. De Benoist, McLean, Egli Cogswell, editors. Worldwide prevalence of anemia 1993–2005: WHO global database on anemia. Vol. 4. Switzerland: WHO; 2008. Haemoglobin thresholds used to define anaemia. 6. Ferraris VA, Ferraris SP. Risk factors for postoperative morbidity. J Thorac Cardiovasc Surg. 1996; 111: 731–738. 7. Rady MY, Ryan T, Starr NJ. Perioperative determinants of morbidity and mortality in elderly patients undergoing cardiac surgery. Crit Care Med. 1998; 26: 225–235. 8. Al Falluji N, Lawrence-Nelson J, Kostis JB, Lacy CR, Ranjan R, Wilson AC. Effect of anemia on 1-year mortality in patients with acute myocardial infarction. Am Heart J. 2002; 144: 636–641. 9. Karkouti K, Wijeysundera DN, Beattie S. Reducing bleeding in cardiac surgery (RBC) investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008;117:478-484. 10.Antonio Miceli,Francesco Romeo,Mattia Glauber,Paolo M de Siena,Massimo Caputo andGianni D Angelin: Preoperative anemia increases mortality and postoperative morbidity after cardiac surgeryJ Cardiothorac Surg. 2014; 9: 137. 11. DeFoe GR, Ross CS, Olmstead EM, Surgenor SD, Fillinger MP, Groom RC, Forest RJ, Pieroni JW, Warren CS, Bogosian ME, Krumholz CF, Clark C, Clough RA, Weldner PW, Lahey SJ, Leavitt BJ, Marrin CA, Charlesworth DC, Marshall P, O'Connor GT. Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg 2001;71:769-776. 12. Kulier A, Levin J, Moser R, Rumpold-Seitlinger G, Tudor IC, SnyderRamos SA, Moehnle P, Mangano DT. Investigators of the Multicenter Study of Perioperative Ischemia Research Group, Ischemia Research and Education Foundation. Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery. Circulation 2007;116:471-479. 13. Cladellas M, Bruguera J, Comín J, Vila J, de Jaime E, Martí J, Gomez M. Is preoperative anaemia a risk marker for in-hospital mortality and
EP
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
Patients: SEMIN 2015 19: 288-292,
AC C
1 2
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
morbidity after valve replacement? Eur Heart J 2006;27:1093-1099. 14. Habib RH, Zacharias A, Schwann TA, Riordan CJ. The independent effects of cardiopulmonary bypass hemodilutional anemia and transfusions on CABG outcomes. Eur J Cardiothorac Surg 2005;28:512-513. 15. Carson JL, Duff A, Poses RM, et al. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet. 1996;348:1055-60. 16. Hardy JF, Martineau R, Couturier A, et al. Influence of haemoglobin concentration after extracorporeal circulation on mortality and morbidity in patients undergoing cardiac surgery. Br J Anaesth. 1998;81 Suppl 1:S3845. 17. Nelson AH, Fleisher LA, Rosenbaum SH. Relationship between postoperative anemia and cardiac morbidity in high-risk vascular patients in the intensive care unit. Crit Care Med. 1993;21:860-6.
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
ACCEPTED MANUSCRIPT
Table 1: Clinical variables among the three groups. Group 3 High HB NO (164)
P value
RI PT
Group 2 Normal HB NO (481)
109 (69.0)% 439 (91.3)%
163 (99.4)%
0.238
Ethnicity Qatari
24 (15.2)%
30 (6.2)%
7 (4.3%)
0.227
Weight >90 kg
30 (19.1)%
78 (16.2)%
21 (12.8)%
0.788
HBA1c >6%
113 (72.4)% 296 (61.5)%
86 (52.4)%
0.32
Creatinine >121 µmol/L
28 (17.7)%
CABG CABG+Valve
83 (52.5)% 50 (31.6)%
Bypass time >120 min Cross clamp time >120 min
M AN U
Sex Male
SC
Group 1 Low HB NO (159)
8 (5.1)%
0.261
318 (66.1)% 73 (15.2)%
104 (63.4)% 33 (20.1)%
0.111 0.171
63 (48.5)%
160 (39.5)%
63 (43.5)%
0.453
19 (15.3)%
40 (10)%
22 (15.2)%
0.677
AC C
EP
TE D
32 (6.6)%
ACCEPTED MANUSCRIPT
Table 2: Postoperative blood transfusion Group3
P Value
Postoperative blood loss > 1liter 31.60%
20%
23.20%
0.006 *
Postoperative PRBCs
69%
58%
Postoperative FFPs
27.80%
Postoperative platelets
74.70%
RI PT
Group2
0.096
18.50%
23.80%
0.23
79.80%
79.30%
0.39
SC
51.85%
M AN U
Group1
Table 3: Postoperative outcome: Variable Group 1 No (159)
Respiratory Complications
15 (9.4)%
TE D
Infections
Group 2 No (481)
Group 3 No (164)
P value
33 (6.9)%
10 (6)%
049
9 (5.5)%
0.227
12 (7.6)%
20 (4.2)%
3 (1.9)%
0
0
ICU Stay >2 days
68(43.3)%
% 138 (28.7)%
40(24.4)%
11 (7.0)%
20 (4.2)%
0
AC C
EP
Acute Renal Failure
ICU re-admission
0.003*
Post-op stay >7 days 111 (70.2)% 211(43.9)% 75(45.8)% 0.0001*
S1110-578X(16)30106-7
DOI:
10.1016/j.jescts.2016.11.004
Reference:
JESCTS 44
To appear in:
Journal of the Egyptian Society of Cardio-Thoracic Surgery
Received Date: 16 October 2016 Accepted Date: 10 November 2016
Please cite this article as: Eltigani A, Abdelaziz A, Kindawy A, Ewila H, Badr A, Elmahrouk A, Preoperative Hemoglobin concentration as an independent predictor for outcome after Coronary Artery Bypass Grafting, Journal of the Egyptian Society of Cardio-Thoracic Surgery (2017), doi: 10.1016/ j.jescts.2016.11.004. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Author group and affiliations Corresponding author: Ahmed Elmahrouk |CARDIOTHORACIC SURGERY DEPARTMENT TANTA UNIVERSITY, Egypt.
AC C
EP
TE D
M AN U
SC
RI PT
Ammar Eltigani (Hamad Medical Corporation), Ayman Abdelaziz (Hamad Medical Corporation), Ali Kindawy (Hamad Medical Corporation), Hesham Ewila (Department of Anesthesia, Suez Canal University, Egypt.), Amr Badr (Cardiology Department, Faculty of Medicine Tanta University)
ACCEPTED MANUSCRIPT
Preoperative Hemoglobin concentration as an independent predictor for outcome after Coronary Artery Bypass Grafting
RI PT
Hesham Ahmed Ewila,* Ammar Eltigani,** Ahmed Elmahrouk,***Ayman Abdelaziz,**** Ali Kindawi**
EP
TE D
M AN U
SC
Introduction: Preoperative anemia is accused for increased complications, morbidity and mortality following cardiac surgery. Due to the nature of cardiac patients who usually have poor myocardium reserve and multiple concomitant comorbidities, it is difficult to identify the role of preoperative hemoglobin concentration in the postoperative outcome. Accordingly, correction of low hemoglobin level prior to cardiac surgery still is a matter of debate. Aim of the work: To determine the impact of preoperative hemoglobin concentration on postoperative outcome following coronary artery bypass grafting. Methods: Data were collected on all patients who underwent coronary artery bypass grafting surgery in our hospital in the last three years. Preoperative Anemia was defined as hemoglobin level below 12 gm. /dl. Accordingly, three groups were identified: low, normal and high preoperative hemoglobin. Postoperative bleeding, red blood cells transfused, myocardial injury, infection rate, lengths of ventilation, renal injury and length of stay in intensive care unit were recorded. Results: We recruited 804 patients in our study. Preoperative anemia were identified in 159 patients assigned in group I. Patients in this group had postoperative blood transfusion in 69% of patients and postoperative bleeding > One liter in 31.6% of patients with P-value of 0.006,0.096 respectively. It showed higher postoperative infection rate in 9.5% of patients (P-value 0.49) and higher length of stay in ICU in 43.3% of patients (P value 0.003). Group II were 481 patients, whom had HB (12.1 -15 gm./dl) showed the shortest postoperative hospital stay in 56.1 % of patients, P value 0.0001. Group III, 164 patients had HB more than 15.1 gm. /dl. No cases of ICU readmission were recorded. Conclusion: -Preoperative hemoglobin level can be used as an indicator of outcome after cardiac surgery. Preoperative anemia should be optimized before coronary artery bypass grafting.
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
Key Words: CABG; Anemia; Predictor of Outcome
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
Introduction: Association between preoperative anemia and increased post-surgical complications has been established in patients undergoing non-cardiac surgery. Such increased risk is attributed to the effect of transfusions and the interactions between the co-morbidities and low hemoglobin levels. Preoperative anemia is a clinically important and increasingly frequent finding in patients presenting for cardiac surgery. In many of these patients, the perioperative risks are inherently high because of multiple concomitant diseases and are particularly aggravated when severe coronary artery disease is present.1–4 According to the World Health Organization (WHO), anemia is defined as hemoglobin level under 12 mg/dl in women and 13 mg/dl in men. 5 Because of their extremely limited coronary reserve, patients undergoing coronary artery bypass grafting (CABG) surgery represent a population potentially most sensitive to the impact of low hemoglobin levels.2,3,6,7 A significant association of anemia with increased perioperative morbidity and mortality has been questioned in a multitude of settings in cardiac surgery.1–8 Anemic patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) have higher morbidity ,mortality, perioperative acute myocardial infarction (AMI) and adverse event rates. 914 However, available data do not describe in details the exact relationship between the percentage of preoperative hemoglobin and the outcomes of CABG patients. In addition, it is unknown whether low hemoglobin levels cause the effects of anemia on outcome per se or by association with other risk factors frequently prevalent in anemic patients.4 Aim of the study: To review the impact of preoperative hemoglobin concentration on postoperative outcome and hemoglobin level as an independent predictor for morbidity and mortality. Methods: We performed a retrospective, descriptive, single-center study with purposive sampling that examined the occurrence of multiple complications after cardiac surgery. Approval for the study was obtained from the ethical committee (reference number 14498/14). After institutional research ethics board approval was obtained, data were retrospectively collected on consecutive adult (>18 years of age) patients who underwent CABG with cardiopulmonary bypass (CPB) from 2011-2014 in Qatar heart hospital, Hamad Medical Corporation. Patients were identified from hospital administrative databases in reverse chronological order starting from January 2014. We collected detailed perioperative,
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
operative and postoperative data (including demographics, laboratory tests, blood product transfusions, cross-clamp time, cardiopulmonary bypass time, postoperative drainage, re-exploration rates, wound infection, postoperative complications, and lengths of stay in the intensive care unit and hospital from existing clinical databases and hospital charts. Data were entered into a computerized database, which was programmed to accept only matching double-entry data falling within pre-specified ranges. All queries were resolved by referring to the patients’ original records. The cohort was distributed according to the preoperative Hemoglobin concentration and divided into three groups: Group I: 159 patients with low preoperative hemoglobin group: HB <12 g/dl. Group II: 481 patients with normal preoperative hemoglobin group: HB 12.1-15 g/dl Group III high: 164 patients with preoperative hemoglobin group: HB > 15 g/dl Exclusion Criteria: Patients who required emergency surgery were excluded from the study. Emergency surgery is always a high-risk procedure and would introduce difficult-to-control variables into the study. Patients who were dialysisdependent were excluded from analyses because chronic kidney disease alters hemoglobin, and anemia in these patients is most likely to be a marker for severity of illness. Similarly, we also excluded patients with impaired myocardial function (EF < 30%). Also excluded were patients with any clinically important bleeding in the last 6 months, recent blood transfusion (less than 2 weeks). If a patient underwent >1 relevant procedure during the study period, only the initial surgery was included for analysis. Dependent Variable: Taking anesthetic induction as the starting time, all clinically relevant outcomes were recorded: Postoperative bleeding, Number of red blood cells units transfused postoperatively, Prolongation of stay in the ICU or the hospital, Surgical wound infection, Acute kidney injury (>2-fold increase in creatinine concentration to above normal levels of 100 µmol/L in women and 110 µmol/L in men or the need for dialysis support). Cerebrovascular events, (any persistent new neurological deficit after surgery) Arrhythmias that includes atrial fibrillation (AF), ventricular tachycardia or ventricular fibrillation. Perioperative myocardial infarction, and use of inotropes (over 24 hours) postoperatively. Death from any cause during hospitalization was also recorded. Results:
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
TE D
M AN U
SC
RI PT
Clinical variables in the groups: We recruited eight hundred and four patients in our study. Patients were divided into three groups according to their preoperative HB concentration. Demographic data showed no significant difference between studied groups. Most of patients were males of non-Qatari ethnicity (table 1). Most of patients included have good preoperative left ventricular function. HBA1c level was higher in low HB level group. Most of patients in all groups underwent the operation with normal creatinine ratio with mild increase in preoperative creatinine level in low HB group. Data showed increase in bypass time in low preoperative HB group (table 1). Postoperative outcomes: Patients in group 1 had postoperative blood transfusion in 69% of patients and postoperative bleeding of more than one liter in 31.6% of patients with P-value of 0.006, 0.096 respectively (table 2). They showed higher postoperative infection rate in 9.5% of patients (P-value 0.49) and higher length of stay in ICU in 43.3% of patients (P value 0.003) (table 3). Group II were showed the shortest postoperative hospital stay in 56.1 % of patients, P value 0.0001. Group III, no cases of ICU readmission were recorded. No difference in respiratory complications between all groups. Three patients in-group 1 showed postoperative renal failure. Two patient proceeded for regular dialysis. No cases of acute postoperative myocardial infarction were recorded in all groups (table 3).
EP
Discussion: Anemia is a clinically important and increasingly frequent preoperative findings. It represents 20 % of patient admitted for cardiac surgery in our hospital. It has been related to increased postoperative complications and mortality. Nappi J (1) emphasized that anemia presence worsens outcomes after cardiac surgery whatever it is a result of a preexisting condition or surgical blood loss. Also Carson JL (2) et al concluded that anemia or intra operative blood loss increases the risk of death or postoperative complications in patients with cardiovascular disease than in those without. Relationship between anemia and postoperative complications after cardiac surgery had been demonestrated, (9,10) as studies failed to establish whether the occurrence of postoperative complications is due to low preoperative hemoglobin level per se or due to confounding effect of transfusions and the interactions between the co-morbidities. More studies are needed as recommended by karkouti et al (9). to investigate either treating preoperative anemia would improve the outcomes of patients undergoing cardiac
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
surgery. Our study was designed to investigate whether preoperative hemoglobin Concentration can be used as independent predictor of mortality and morbidity following coronary artery bypass grafting. We recruited 159 out of 803 patients who had preoperative anemia as hemoglobin level was below 12 gm/dl according to WHO definitions. Ferraris et al (6) suggest that older patients with preoperative anemia are at increased risk for postoperative complications, which was not clear in our study. As the mean age in the preoperative anemic patients group was 58 years. There were no significant differences between patient age in this group and ages in normal and high preoperative hemoglobin groups. Numerous preoperative risk factors may raise the propensity of postoperative complications in patients undergoing cardiac surgery: Poor cardiac functions, presence of diabetes mellitus, presence of hypertension and poor preoperative renal function. The extent of preexisting comorbidities substantially affects perioperative anemia tolerance Kulier A. (12) In our study, all patients were ASA physical status III–IV and Euro score, which we use to identify risks for morbidity and mortality, found to be matched in all groups. There are significant independent adverse effects of CPB hemodilutional anemia and intraoperative red blood cells transfusions on postoperative outcomes. In our study the 48.5 % of patients in the preoperative anemia group had prolonged bypass time more than 120 minutes but there were no significant differences when comparing to other groups. Regarding to postoperative outcome, Preoperative anemia is independently associated with adverse outcomes after cardiac surgery karkouti et al (9). which was clear in our study as patients in low preoperative hemoglobin group showed high incidence of postoperative blood transfusion in 69% of patients and it was statistically significant “P value 0.096” when comparing with patients in normal or high preoperative hemoglobin. Postoperative bleeding also was higher in this group as 31.6 % of patients bled more than one liter in the first 24 hours. Patients with low preoperative hemoglobin showed higher postoperative infection rate in 9.5% of patients (P-value 0.49) in comparison to other groups. Three patients in this group showed postoperative renal failure while two of them proceeded for regular dialysis. No cases of acute postoperative renal failure reported in the other groups. As postoperative anemia may play a role in postoperative myocardial ischemia and cardiac morbidity Nelson AH et al (17).
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
surprisingly we did not record any cases of acute postoperative myocardial ischemia or infarction was recorded in all groups. Patients with preoperative anemia recorded the higher length of stay in ICU in 43.3% of patients (P value 0.003) when compared to other groups while patients with normal preoperative hemoglobin had the shortest postoperative hospital stay as 56.1 % of patients, (P value 0.0001) discharged from the hospital less than one week postoperatively. Patients with high preoperative hemoglobin group (Hb > 15 gm/dl) did not record any intensive care readmission while in preoperative anemia group 5% of patients readmitted back to ICU. Zindrou et al (3) noted that low preoperative hemoglobin concentration of had a five-fold higher in-hospital mortality rate after surgery than those with a higher hemoglobin concentration, Which was coincided with our results as patients with low preoperative HB group had the higher mortality rate in 7.5% of patients while mortality rate was 3.5% in normal preoperative Hb group and 1.8 % of patients in high preoperative Hb group. So from our experience in Qatar heart hospital we can emphasize that preoperative hemoglobin concentration can be used as independent predictor of postoperative outcome following coronary artery bypass grafting. Optimization of preoperative hemoglobin is recommended to alleviate the burden of confounding preoperative risk factors and decrease postoperative adverse events Conclusion: The results of our study confirmed that preoperative hemoglobin level can be utilized as an independent predictor of morbidity and mortality following cardiac surgery. Therefore, we recommend that preoperative hemoglobin should be optimized prior to surgery whenever it is possible. Study strength and limitations References: 1. Nappi J. Anemia in patients with coronary artery disease. Am J Health Syst Pharm. 2003; 60: S4–S8. 2. Carson JL, Duff A, Poses RM, Berlin JA, Spence RK, Trout R, Noveck H, Strom BL. Effect of anemia and cardiovascular disease on surgical mortality and morbidity. Lancet. 1996; 348: 1055–1060. 3. Zindrou D, Taylor KM, Bagger JP. Preoperative hemoglobin concentration and mortality rate after coronary artery bypass surgery. Lancet. 2002; 359: 1747– 1748. 4. G. lobel, M. Javidroozi, A.Shander: Risk of Anemia in cardiac Surgery
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
ACCEPTED MANUSCRIPT
CARDIOTHORAC
VASC
ANESTH
December
TE D
M AN U
SC
RI PT
5. De Benoist, McLean, Egli Cogswell, editors. Worldwide prevalence of anemia 1993–2005: WHO global database on anemia. Vol. 4. Switzerland: WHO; 2008. Haemoglobin thresholds used to define anaemia. 6. Ferraris VA, Ferraris SP. Risk factors for postoperative morbidity. J Thorac Cardiovasc Surg. 1996; 111: 731–738. 7. Rady MY, Ryan T, Starr NJ. Perioperative determinants of morbidity and mortality in elderly patients undergoing cardiac surgery. Crit Care Med. 1998; 26: 225–235. 8. Al Falluji N, Lawrence-Nelson J, Kostis JB, Lacy CR, Ranjan R, Wilson AC. Effect of anemia on 1-year mortality in patients with acute myocardial infarction. Am Heart J. 2002; 144: 636–641. 9. Karkouti K, Wijeysundera DN, Beattie S. Reducing bleeding in cardiac surgery (RBC) investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008;117:478-484. 10.Antonio Miceli,Francesco Romeo,Mattia Glauber,Paolo M de Siena,Massimo Caputo andGianni D Angelin: Preoperative anemia increases mortality and postoperative morbidity after cardiac surgeryJ Cardiothorac Surg. 2014; 9: 137. 11. DeFoe GR, Ross CS, Olmstead EM, Surgenor SD, Fillinger MP, Groom RC, Forest RJ, Pieroni JW, Warren CS, Bogosian ME, Krumholz CF, Clark C, Clough RA, Weldner PW, Lahey SJ, Leavitt BJ, Marrin CA, Charlesworth DC, Marshall P, O'Connor GT. Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group. Ann Thorac Surg 2001;71:769-776. 12. Kulier A, Levin J, Moser R, Rumpold-Seitlinger G, Tudor IC, SnyderRamos SA, Moehnle P, Mangano DT. Investigators of the Multicenter Study of Perioperative Ischemia Research Group, Ischemia Research and Education Foundation. Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery. Circulation 2007;116:471-479. 13. Cladellas M, Bruguera J, Comín J, Vila J, de Jaime E, Martí J, Gomez M. Is preoperative anaemia a risk marker for in-hospital mortality and
EP
3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
Patients: SEMIN 2015 19: 288-292,
AC C
1 2
ACCEPTED MANUSCRIPT
EP
TE D
M AN U
SC
RI PT
morbidity after valve replacement? Eur Heart J 2006;27:1093-1099. 14. Habib RH, Zacharias A, Schwann TA, Riordan CJ. The independent effects of cardiopulmonary bypass hemodilutional anemia and transfusions on CABG outcomes. Eur J Cardiothorac Surg 2005;28:512-513. 15. Carson JL, Duff A, Poses RM, et al. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet. 1996;348:1055-60. 16. Hardy JF, Martineau R, Couturier A, et al. Influence of haemoglobin concentration after extracorporeal circulation on mortality and morbidity in patients undergoing cardiac surgery. Br J Anaesth. 1998;81 Suppl 1:S3845. 17. Nelson AH, Fleisher LA, Rosenbaum SH. Relationship between postoperative anemia and cardiac morbidity in high-risk vascular patients in the intensive care unit. Crit Care Med. 1993;21:860-6.
AC C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
ACCEPTED MANUSCRIPT
Table 1: Clinical variables among the three groups. Group 3 High HB NO (164)
P value
RI PT
Group 2 Normal HB NO (481)
109 (69.0)% 439 (91.3)%
163 (99.4)%
0.238
Ethnicity Qatari
24 (15.2)%
30 (6.2)%
7 (4.3%)
0.227
Weight >90 kg
30 (19.1)%
78 (16.2)%
21 (12.8)%
0.788
HBA1c >6%
113 (72.4)% 296 (61.5)%
86 (52.4)%
0.32
Creatinine >121 µmol/L
28 (17.7)%
CABG CABG+Valve
83 (52.5)% 50 (31.6)%
Bypass time >120 min Cross clamp time >120 min
M AN U
Sex Male
SC
Group 1 Low HB NO (159)
8 (5.1)%
0.261
318 (66.1)% 73 (15.2)%
104 (63.4)% 33 (20.1)%
0.111 0.171
63 (48.5)%
160 (39.5)%
63 (43.5)%
0.453
19 (15.3)%
40 (10)%
22 (15.2)%
0.677
AC C
EP
TE D
32 (6.6)%
ACCEPTED MANUSCRIPT
Table 2: Postoperative blood transfusion Group3
P Value
Postoperative blood loss > 1liter 31.60%
20%
23.20%
0.006 *
Postoperative PRBCs
69%
58%
Postoperative FFPs
27.80%
Postoperative platelets
74.70%
RI PT
Group2
0.096
18.50%
23.80%
0.23
79.80%
79.30%
0.39
SC
51.85%
M AN U
Group1
Table 3: Postoperative outcome: Variable Group 1 No (159)
Respiratory Complications
15 (9.4)%
TE D
Infections
Group 2 No (481)
Group 3 No (164)
P value
33 (6.9)%
10 (6)%
049
9 (5.5)%
0.227
12 (7.6)%
20 (4.2)%
3 (1.9)%
0
0
ICU Stay >2 days
68(43.3)%
% 138 (28.7)%
40(24.4)%
11 (7.0)%
20 (4.2)%
0
AC C
EP
Acute Renal Failure
ICU re-admission
0.003*
Post-op stay >7 days 111 (70.2)% 211(43.9)% 75(45.8)% 0.0001*