ICU Rounds Report - The Trouble with Transfusions

When to give blood continues to perplex. In the past we've blogged about paucity of good, randomized data to help decided transfusion triggers. Now, surgeons have added yet another retrospective study showing potentially big problems with transfusion. Looking at over 10,000 patients in the American College of Surgery National Surgical Quality Program database, the authors found giving one or two units of blood was associated with greater chance of death  (odds ratio [OR], 1.29; 95% CI, 1.03–1.62) or a bad complication: pulmonary (OR, 1.76; 95% CI, 1.48–2.09), septic (OR, 1.43; 95% CI, 1.21–1.68), thromboemoblic (OR, 1.77; 95% CI, 1.32–2.38) or wound (OR, 1.87; 95% CI, 1.47–2.37).

The amount retrospective data in this area seems to grow every month. Unfortunately, there hasn't been a parallel increase in clinically useful data from RTCs. To review, here is a partial list of some big retrospective papers. Again and again, these reviews find transfusion of PRBCs is harmful in most of our common situations. Every trial makes some attempt at controlling for relevant co-morbidities, but controlling here is impossible. No one can say why the transfused group did worse - was it from the transfusion or the process that lead to it?  Remember, only the TRICC and TRACS trial have been well conducted and randomized.

In Critically Ill patients:
"For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P = .02); the Kaplan-Meier log-rank test confirmed this difference"
Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D: Anemia and blood transfusion in critically ill patients. JAMA 2002; 288:1499–507

"Transfusion practice has changed little during the past decade. The number of RBC units transfused is an independent predictor of worse clinical outcome."
Corwin HL, et al. The CRIT Study: Anemia and blood transfusion in the critically ill—current clinical practice in the United States. Crit Care Med 2004; 32:39–52

"Despite the inherent limitations in the analysis of cohort studies, our analysis suggests that in adult, intensive care unit, trauma, and surgical patients, RBC transfusions are associated with increased morbidity and mortality and therefore, current transfusion practices may require reevaluation."
Marik PE, et al. Efficacy of erythrocytes transfusion in the critically ill: A systematic review of the literature. Crit Care Med 2008; 36:2667–74

Perioperatively:
"Intraoperative blood transfusion is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia."
Glance LG, et al. Association between Intraoperative Blood Transfusion and Mortality and Morbidity in Patients Undergoing Noncardiac Surgery. Anesthsiology 2011; 114(2):283-292

In Cardiac Surgery
"Perioperative red blood cell transfusion is the single factor most reliably associated with increased risk of postoperative morbid events after isolated coronary artery bypass grafting. Each unit of red cells transfused is associated with incrementally increased risk for adverse outcome"
Koch CG, et al. Morbidity and mortality risk associated with erythrocytes and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006; 34:1608–16

"Exposure to both hemodilutional anemia and RBC transfusion during surgery are associated with increased risk of low-output heart failure (LOF), defined as placement of an intraoperative or postoperative intra-aortic balloon pump, return to CPB after initial separation, or treatment with multiple pressors."
Surgenor SD, et al. Intraoperative erythrochites transfusion during coronary artery bypass graft surgery increases the risk of postoperative low-output heart failure. Circulation 2006; 114:I43–8

"Exposure to 1 or 2 U of RBCs was associated with a 16% increased hazard of decreased survival after cardiac surgery"
Surgenor SD, et al. The association of perioperative erythrochites transfusions and decreased long-term survival after cardiac surgery. Anesth Analg 2009; 108:1741–6

"Red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs."
Murphy GJ, et al. Increased mortality, postoperative morbidity, and cost after erythrochites transfusion in patients having cardiac surgery. Circulation 2007; 116:2544–52

In Trauma:
"Blood transfusion is confirmed as an independent predictor of mortality, ICU admission, ICU LOS, and hospital LOS in trauma after controlling for severity of shock by admission base deficit, lactate, shock index, and anemia."
Malone DL, et al. Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma 2003; 54:898–905

"Red blood cell transfusion within the first 24 hours following admission is associated with an increase in mortality in pediatric trauma patients"
Stone, TJ, et al.  Red blood cell transfusion within the first 24 hours of admission is associated with increased mortality in the pediatric trauma population: a retrospective cohort study. J Trauma Mngmnt 2008, 2:9

During Acute Coronary Syndrome:
"Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality, and this relationship persists after adjustment for other predictive factors and timing of events. We suggest caution regarding the routine use of blood transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease."
Rao SV, et al. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA 2004; 292:1555–62

"Patients who undergo transfusion are sicker at baseline and experience a higher risk of adverse outcomes than their nontransfused counterparts."
Yang X, et al.  The implications of blood transfusions for patients with non-ST-segment elevation acute coronary syndromes: Results from the CRUSADE National Quality Improvement Initiative. J Am Coll Cardiol 2005; 46:1490–5

"Transfusion in anemic patients admitted with suspected acute coronary syndrome/non–ST-elevation MIs led to a significant increase in 30-day recurrent MI or death (odds ratio 3.05, 95% confidence interval 1.80 to 5.17, p <0.001). This relation persisted after adjusting for significant univariate predictors: hypotension on presentation, pulmonary edema, and increased troponin-I levels (odds ratio 2.57, 95% confidence interval 1.41 to 4.69, p <0.001)."
Singla I, et al. Impact of blood transfusions in patients presenting with anemia and suspected acute coronary syndrome. Am J Cardiol 2007; 99:1119–21

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Jordan Hackworth, M.D.

Fellow, Critical Care Medicine
Department of Anesthesiology
University of Virginia
PO Box 800710
Charlottesville, VA 22908-0710
T (434) 924-2283
F (434) 982-0019

ICU Rounds Report - Nicotine patches and 24-hr staffing

From Daniel:
Nicotine Patches for the Perioperative Smoker? Nicotine replacement therapy (NRT) has been used in the inpatient setting to decrease cravings and lower psychological stress, but does it work perioperatively?  David Warner and friends performed a double-blind placebo controlled trial of 121 smokers undergoing elective surgical procedures and found no benefit whatsoever.  They measured Nicotine Withdrawal Scores and the Perceived Stress Scores for patients perioperatively receiving placebo vs. nicotine patches (all P > 0.19).  This contrasts to a much smaller study in healthy non-surgical volunteers where the patch was shown to reduce cravings.

Acutely, nicotine is known to have adverse effects on wound healing, lung function, immunity and may increase cardiovascular events. No perioperative studies have been done looking at NRT and these relevant outcomes- infections, healing, MI's, pulmonary complications, etc. (Although it should be noted that NRT appears safe for outpatients with known cardiovascular disease).That said, the theoretic potential for harm is real while the available data suggest that if you're jonesing for a light after surgery, the patch probably isn't going to help anyway. Further, at least 2 additional studies have found the NRT has no meaningful effect on post-operative pain scores. So, why not then just avoid them?

Joseph et al.  The safety of the transdermal nicotine as an aid to smoking cessation in patients with cardiac disease.  1996.  N. Engl. J. Med.; 335: 1792.
Teneggi et al.  Smokers deprived of cigarettes for 72 h: effect of nicotine patches on craving and withdrawal.  2002.  Psychopharmacology; 164(2): 177-87.
Warner et al.  Effect of nicotine replacement therapy on stress and smoking behaviour in surgical patients.  2005.  Anesthesiology; 102(6): 1138-46.

Is 24-hour staffing worth the trouble? It's been known for a long time that outcomes vary widely by ICU. Admission to a high quality ICU can lower your risk of death by 40%. So, what makes a good ICU? That's the subject of intense research and debate, but adherence to evidence-based national guidelines, wide-spread use of protocols, adequate multidisciplinary staffing and 24-hour in-house intensivist staffing are generally acknowledged as the benchmarks that make a high quality ICU.

Just up the Mason-Dixon line, the University of Maryland (UM) recently completed a large hospital renovation that included a brand new, larger MICU (from 10 to 29 beds). But in addition to the new facilities, they started 24-hour in-house attending coverage (previously a fellow and 2 residents were on overnight), added a pharmacist on rounds and changed RT staffing ratios from 1:24 to 1:10. Prior to the change, the UM MICU was considered "high quality" and in fact had been honored by the Leapfrog Group for superior outcomes.

The results were big. Relative ICU mortality dropped by 19% (18.4% to 14.9%, p<.006) meaning one in five deaths were prevented. Patients were vent free longer and received less fentanyl and versed. Is this intervention feasible? Who knows, they didn't do a cost analysis. Is it generalizable? Probably not, many of the interventions were specific to UM and all done at the same time. Does it show that thoughtful attention to ICU organization can make as big a difference in outcome as many of our equally costly clinical interventions? Absolutely.

Kahn JM, Goss CH, Heagerty PJ, et al: Hospital volume and the outcomes of mechanical ventilation. N Engl J Med 2006; 355: 41–50
Netzer G, et al. Decreased mortality resulting from a multicomponent intervention in a tertiary care medical intensive care unit Crit Care Med Feb 2011 39(2):284-293,.

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Jordan Hackworth, M.D.

Fellow, Critical Care Medicine

Department of Anesthesiology

University of Virginia

PO Box 800710

Charlottesville, VA 22908-0710

T (434) 924-2283

F (434) 982-0019