A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries.

BACKGROUND: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. METHODS: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. RESULTS: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. CONCLUSIONS: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

In Vivo Protamine Titration Using Activated Coagulation Time to Neutralize Heparin Anticoagulation in Cardiac Surgery: Proof of Concept.

OBJECTIVE: In vivo protamine titration (IVPT) is based on the observation of a plateau on the decay curve of the celite activated clotting times (ACTs) during protamine infusion for heparin reversal. The aim of the present study was to determine the optimal protamine/heparin ratio to reverse anticoagulation using IVPT curves. DESIGN: Prospective, randomized study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 138 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: The control group was given a protamine infusion of 1.3 mg per 1 mg (100 U) of heparin over 21 minutes. ACT was measured every 3 minutes. In the test group, the protamine dose was prepared using the same ratio as for the control group, and ACT values were measured every 3 minutes until a plateau was reached (2 consecutive ACT values <160 s), at which time the protamine infusion was stopped. The protamine/heparin ratio, blood losses, transfusions, and heparin concentrations were recorded. RESULTS: The protamine dose was lower in the test group (456.00 ± 105.66 mg [control group] v 295.25 ± 100.60 mg [test group]; p < 0.0001). The mean protamine/heparin ratios were 1.30 ± 0.10 (control group) and 0.81 ± 0.22 (test group) (p < 0.0001). Heparin concentrations were greater in the test group 15 minutes (0.10 [0-0.2] U/mL v 0 [0-0.1] U/mL; p = < 0.0001) and 3 hours (0 [0-0.1] U/mL v 0 [0-0] U/mL; p = 0.0002) after protamine infusion. There was no difference in the blood losses and transfusion requirements. CONCLUSIONS: IVPT is safe and efficient in this low-risk population.

"CAPS" Cardiac Acute Pain Services-A Nationwide Survey From Canada.

OBJECTIVES: Acute Pain Services (APS) are well-established worldwide; however, their availability and use in cardiac surgery units are less widespread and, even where present, may be provided less consistently. The authors undertook this survey to assess the current organization of Cardiac Acute Pain Services (CAPS) in Canada. DESIGN: This was a prospectively administered survey. SETTING: This study included all centers in Canada that conducted adult cardiac surgery. PARTICIPANTS: The participants were anesthesiologists. INTERVENTION: A 20-item questionnaire covered the demographics, functioning and APS structure. RESULTS: The authors achieved a response rate of 100% with completed questionnaires from all 31 centers. Ten centers (32.3%) stated that they had a dedicated CAPS, 9 centers (29%) stated that they did not have an APS, and 12 centers (38.7%) had APS but no CAPS. At the time of the survey for the 10 centers with CAPS, 3 of the CAPS had a physician-run model, 4 had a combined physician and nurse service, and 1 used a combination of protocols, intensivists, and nurse practitioners. Nine centers had an anesthesiologist assigned to daily acute pain rounds. Only in 2 of 10 centers with CAPS were more than 50% of their cardiac surgery patients receiving care. In general, postoperative pain management was a protocol-driven activity. CONCLUSIONS: CAPS are varied in both structure and functioning. Further work is required both at the institutional and the national levels to improve the postoperative care and the pain-related outcomes of patients undergoing cardiac surgery.

Development of a specific algorithm to guide haemostatic therapy in children undergoing cardiac surgery: a single-centre retrospective study.

BACKGROUND: Although rotational thromboelastometry (ROTEM) is increasingly used to guide haemostatic therapy in a bleeding patient, there is a paucity of data guiding its use in the paediatric population. OBJECTIVE: The objective of this study is to develop an algorithm on the basis of ROTEM values obtained in our paediatric cardiac population to guide the management of the bleeding child. DESIGN: A retrospective analysis. SETTING: Department of Anaesthesiology, Queen Fabiola Children's University Hospital. Data were collected between September 2010 and January 2012. PATIENTS: All children who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB) were reviewed. INTERVENTION: None. MAIN OUTCOME MEASURES: Significant postoperative bleeding was defined as blood loss more than 10% of the child's estimated blood volume within the first six postoperative hours, dividing our population according to high blood loss (HBL) or low blood loss (LBL). Factors independently associated with postoperative bleeding determined the bleeding probability. Receiving operating characteristics (ROC) curves were constructed with the aim of determining relevant ROTEM parameters (including clot amplitude 10 min after administration of protamine [A10]) to be used in our algorithm. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were determined for the developed algorithm. RESULTS: One-hundred and fifty children were included in our study. Univariate and multivariate logistic regression analysis revealed that preoperative weight (kg), presence of a cyanotic disease (yes/no) and wound closure duration (min) were independent predictors of postoperative bleeding. Analysis of our ROTEM parameters revealed that clotting time (CT) ≥ 111 s, A10 ≤ 38 mm measured on the EXTEM and A10 ≤ 3 mm obtained on the FIBTEM tests were the three relevant parameters to guide haemostatic therapy. If the ROTEM-based algorithm was applied according to the bleeding risk (n = 65), 27 out of 29 of the HBL and 24 out of 36 of the LBL group would have been treated. CONCLUSION: This study describes an algorithm starting with the detection of abnormal bleeding in which ROTEM could be used to guide haemostatic therapy in bleeding children after CPB. Further studies are needed to test the efficacy of this specific algorithm-based approach.

Efficacy and safety of activated recombinant factor VII in cardiac surgical patients.

PURPOSE OF REVIEW: Excessive bleeding is a common and morbid problem after cardiac surgery. There is no doubt a need for an effective and safe hemostatic agent in order to minimize transfusions and avoid surgical reintervention for hemostasis. Recombinant activated factor VII (rFVIIa) is being used (off-label) increasingly after cardiac surgery to prevent or to control hemorrhage, but its efficacy and safety remain unclear. RECENT FINDINGS: Several case reports, case series and registries would tend to support the use of activated recombinant factor VII to control excessive bleeding after cardiac operations. On the contrary, two randomized controlled trials have produced negative results whereas a third has not been published yet. Adverse thrombotic events are reported with increasing frequency. SUMMARY: At present, the generalized use of rFVIIa to prevent or to control excessive bleeding after cardiac surgery cannot be recommended. The decision to administer a potent hemostatic such as rFVIIa outside its recognized prescribing indications should be made with caution by well informed physicians and discussed with the patient. Patients should be informed about knowledge gaps and pertinent risks, which are both important in the case of rFVIIa.

Efficacy and safety of recombinant activated factor VII to control bleeding in nonhemophiliac patients: a review of 17 randomized controlled trials.

We reassess all published randomized controlled trials that have evaluated the hemostatic efficacy or safety of recombinant activated factor VII (rFVIIa), or both, in nonhemophiliac patients. Seventeen trials published in 16 articles dealt either with the prophylactic (nine trials) or the therapeutic (eight trials) use of rFVIIa to prevent or to treat excessive bleeding. At present, the role of rFVIIa to prevent or to control bleeding and reduce transfusions in various patient populations remains unclear. In addition, the safety of rFVIIa remains a concern. Consequently, we conclude that the generalized use of rFVIIa to prevent or to control bleeding in nonhemophiliac patients can not be recommended.

Effect of intravenous nitroglycerin on cerebral saturation in high-risk cardiac surgery.

PURPOSE: To determine whether or not intravenous nitroglycerin (IV NTG) can prevent a decrease in near-infrared spectroscopy (NIRS) values during cardiopulmonary bypass (CPB). METHODS: We conducted a randomized double-blinded study in a tertiary academic center including 30 patients with a Parsonnet score>or=15 scheduled for a high-risk cardiac surgery. The patients were randomized to receive either IV NTG (initial dose of 0.05 microg.kg(-1).min(-1), followed by 0.1 microg.kg(-1).min(-1)) or placebo after anesthetic induction until the end of CPB. The primary outcome was a decrease of 10% in NIRS values during CPB. RESULTS: Despite the absence of between-group difference in the mean cerebral oxygen saturation during CPB, there was a significant decrease in NIRS values during CPB in the placebo group, whereas mean NIRS values were maintained in the IV NTG group (-16.7% vs 2.3% in the NTG, P=0.019). Major hemodynamic variables were similar at corresponding time periods in both groups, while patients in the IV NTG group had higher CK-MB values and experienced greater blood loss during the first 24 hr postoperatively. CONCLUSION: Intravenous nitroglycerin administration before and during CPB may prevent a decrease in NIRS values associated with CPB in high-risk cardiac surgery. Further studies are warranted to determine the efficacy and the risks associated with IV NTG infusion for this indication during CPB in high-risk patients.

Erythropoietic response to two epoetin alfa regimens in critically ill patients: a pilot study.

STUDY OBJECTIVE: To compare the erythropoietic responses and tolerability of two recombinant human erythropoietin (EPO) regimens. DESIGN: Prospective, open-label, multicenter study. SETTING: Three multidisciplinary intensive care units in Québec, Canada. PATIENTS: Sixty critically ill patients. INTERVENTION: The first 30 patients received EPO 40,000 U/week (group A); the next 30 received 40,000 U twice/week (group B). MEASUREMENTS AND MAIN RESULTS: Percent change from baseline in reticulocyte count and hemoglobin concentration were evaluated in both groups on study days 7 and 14. The numbers of adverse events were also compared between the two groups. No statistically significant differences were found in the results between the two groups. CONCLUSION: Although the study had limitations, it suggested that EPO 40,000 U twice/week did not increase or sustain stimulation of the erythropoietic response compared with EPO 40,000 U/week in critically ill patients.

Antithrombotic therapy in cardiac surgery.

PURPOSE: To review the perioperative management of antithrombotic therapy in cardiac surgery, including the management of cardiopulmonary bypass (CPB) and off-pump surgery. METHODS: A review of the relevant English literature over the period 1975-2005 was undertaken, in addition to a review of international practices in antithrombotic therapy in cardiac surgery. PRINCIPAL FINDINGS: Cardiopulmonary bypass is required in most procedures and makes anticoagulation mandatory. Anticoagulation is, usually, achieved with unfractionnated heparin (UFH). Unfractionated heparin is monitored by point-of-care (POC) testing, such as the activated clotting time or the determination of heparin concentration. The target values of both tests remain empirical, with no clearly validated thresholds. The target value needs to be adjusted according to the POC test, given significant variations between devices and activators. After CABG, the need for antiplatelet therapy is well demonstrated, in order to limit the risk of postoperative death or ischemic events, and improve venous graft patency. Immediately after valvular surgery, antithrombotic therapy should take into account the specific risk carried by each patient and by each prosthetic device. The risk of venous thromboembolism, though poorly defined, is also present in the postoperative period and may require additional attention. Given the frequent exposure to UFH, occurrence of heparin-induced thrombocytopenia is not infrequent in these patients and requires careful individual management. CONCLUSIONS: Antithrombotic therapy is an essential component of cardiac surgery. Yet, with the exception of antiplatelet agents in CABG patients, antithrombotic therapy is often based on the clinical experience of medical teams more than on an evidence-based assessment of the literature.

Importance of relative pulmonary hypertension in cardiac surgery: the mean systemic-to-pulmonary artery pressure ratio.

OBJECTIVE: To determine the importance of the mean arterial pressure-to-mean pulmonary artery pressure ratio (MAP/MPAP) in cardiac surgical patients. DESIGN: Retrospective and prospective studies (3 groups). SETTING: Tertiary care hospital. PARTICIPANTS: Cardiac surgical patients (1,557). INTERVENTION: Retrospective analysis (group 1), induction of general anesthesia (group 2), and transesophageal Doppler echocardiography (group 3). MEASUREMENTS AND MAIN RESULTS: In group 1 (n = 1,439), demographic, hemodynamic, and other perioperative variables were collected with follow-up until hospital discharge. The primary outcome was a composite index of hemodynamic complications that included death, resuscitated cardiac arrest, use of vasopressive drugs for >24 hours postoperatively, or the use of an intra-aortic balloon pump that was not present preoperatively. In group 2 (n = 34), the effect of general anesthesia on the MAP/MPAP ratio was studied, and Doppler echocardiography was used to evaluate diastolic profiles in group 3 (n = 74). In group 1, a total of 302 patients experienced hemodynamic complications (21%). The MAP/MPAP ratio was significantly lower in the patients who developed complications (3.3 +/- 1.3 v 4.0 +/- 1.4, p < 0.0001). Multiple stepwise logistic regression analysis showed the MAP/MPAP ratio to be an independent predictor of hemodynamic complications (p < 0.0001). In group 2, the induction of anesthesia decreased both MAP and MPAP, but the ratio remain unchanged (p = 0.242). In group 3, patients with moderate-to-severe diastolic dysfunction (DD) had a lower ratio (3.5 +/- 0.9 v 4.0 +/- 1.1 compared with those with normal-to-mild DD, p = 0.07). CONCLUSION: The MAP/MPAP ratio is a useful hemodynamic variable in cardiac surgery. It can be used to predict hemodynamic complications after cardiac surgery, is not influenced by the induction of anesthesia, and tends to correlate with the severity of left ventricular diastolic profiles.

Prevalence, characteristics, and predictors of chronic nonanginal postoperative pain after a cardiac operation: a cross-sectional study.

OBJECTIVE: This study was designed to assess the prevalence, characteristics, effect, and predictors of chronic postoperative pain 1 to 3 years after cardiac surgery. METHODS: Seven hundred thirty-six patients who underwent coronary artery bypass surgery, valve replacement, or both between 1999 and 2002 were mailed questionnaires (response rate, 79% [n = 579]; 564 questionnaires were analyzed), and their hospital records were reviewed. RESULTS: Nonanginal chronic postoperative pain affected 23% of patients. Eighty percent of them had pain 1 or more days per week. The worst and usual pain intensities during the week preceding the survey reached moderate to severe levels (> or =4/10) in more than half of the patients. Thirty-one percent of the patients with chronic postoperative pain had taken analgesic pain medication during that week. During the same period, pain interfered significantly (> or =4/10) with various aspects of patients' daily life (eg, general activity level: 39.1%, sleep: 36.7%). When patients with and without chronic postoperative pain were compared, the former group had significantly higher levels of anxiety and depression, and they perceived their health-related quality of life as more compromised. Multivariate logistic regression analysis revealed that greater analgesic needs in the first few days postoperatively were associated with an increased risk of chronic postoperative pain. The only other significant factor was the time elapsed from surgical intervention to survey: the longer it was, the less likely the patients were to report chronic postoperative pain. CONCLUSION: The prevalence, severity, and effect of chronic postoperative pain after cardiac surgery should not be underestimated. Longitudinal prospective studies are needed to further evaluate risk factors, including inadequate postoperative pain relief in the acute period.

Mixed venous blood gas sampling is not influenced by the speed of withdrawal in cardiac surgery patients.

OBJECTIVE: To determine whether mixed venous blood gas sampling obtained by pulmonary artery catheter (PAC) is influenced by the speed of withdrawal. DESIGN: Prospective, observational study. SETTING: Surgical intensive care unit at a university hospital. SUBJECTS: Twenty-five patients in the early postoperative period of cardiac surgery. MEASUREMENTS AND MAIN RESULTS: After verification of the adequate position of the PAC, measurements of mixed venous blood gas oxygen saturation, oxygen partial pressure (PO(2)), carbon dioxide partial pressure (PCO(2)), pH and bicarbonates were obtained at two different rates of withdrawal. A slow sampling was taken at a mean speed of 3 ml/min and a fast sampling at 18 ml/min for each patient. The mean difference in venous oxygen saturation between slow and fast samplings was -0.18+/-1.3%, venous PO(2): -0.2+/-1.3 mmHg, venous PCO(2): 0.1+/-0.9 mmHg, venous pH: 0+/-0.03, venous bicarbonates: 0.03+/-0.5 mmol/l. CONCLUSION: Using the Bland & Altman method, we showed a satisfactory agreement between slow and fast mixed venous blood gas sampling techniques when measuring PO(2), oxygen saturation, PCO(2), pH and bicarbonates though a PAC.

Can peripheral venous pressure be interchangeable with central venous pressure in patients undergoing cardiac surgery?

OBJECTIVE: Pressure measurements at the level of the right atrium are commonly used in clinical anesthesia and the intensive care unit (ICU). There is growing interest in the use of peripheral venous sites for estimating central venous pressure (CVP). This study compared bias, precision, and covariance in simultaneous measurements of CVP and of peripheral venous pressure (PVP) in patients with various hemodynamic conditions. DESIGN AND SETTING: Operating room and ICU of a tertiary care university-affiliated hospital. PATIENTS: Nineteen elective cardiac surgery patients requiring cardiopulmonary bypass were studied. INTERVENTIONS: A PVP catheter was placed in the antecubital vein and connected to the transducer of the pulmonary artery catheter with a T connector. Data were acquired at different times during cardiac surgery and in the ICU. MEASUREMENTS AND RESULTS: A total of 188 measurements in 19 patients were obtained under various hemodynamic conditions which included before and after the introduction of mechanical ventilation, following the induction of anesthesia, fluid infusion, application of positive end expiratory pressure and administration of nitroglycerin. PVP and CVP values were correlated and were interchangeable, with a bias of the PVP between -0.72 and 0 mmHg compared to the CVP. CONCLUSIONS: PVP monitoring can accurately estimate CVP under various conditions encountered in the operating room and in the ICU.

Inhaled epoprostenol (prostacyclin) and pulmonary hypertension before cardiac surgery.

OBJECTIVE: Pulmonary hypertension is commonly found in patients undergoing valvular surgery and can be worsened by cardiopulmonary bypass. Inhaled epoprostenol (prostacyclin) has been used for the treatment of pulmonary hypertension, but its effects compared with those of placebo on hemodynamics, oxygenation, echocardiographic examination, and platelet function have not been studied during cardiac surgery. METHODS: Twenty patients with pulmonary hypertension undergoing cardiac surgery were randomized in a double-blind study to receive inhaled epoprostenol (60 microg) or placebo. The inhalation occurred after induction of anesthesia and before surgical incision. The effects on left and right systolic and diastolic cardiac functions evaluated by means of pulmonary artery catheterization and transesophageal echocardiography, as well as oxygenation and platelet aggregation, were studied. RESULTS: Inhalation of epoprostenol significantly reduced indexed right ventricular stroke work from 10.7 +/- 4.57 g. m. m(-2) to 7.8 +/- 3.94 g. m. m(-2) (P =.003) and systolic pulmonary artery pressure from 48.4 +/- 18 mm Hg to 38.9 +/- 11.9 mm Hg (P =.002). The effect was correlated with the severity of pulmonary hypertension (r = 0.76, P =.01) and was no longer apparent after 25 minutes. There was no significant effect on systemic arterial pressures, left ventricular function, arterial oxygenation, platelet aggregation, and surgical blood loss. CONCLUSION: Inhaled epoprostenol reduces pulmonary pressure and improves right ventricular stroke work in patients with pulmonary hypertension undergoing cardiac surgery. A dose of 60 microg is hemodynamically safe, and its effect is completely reversed after 25 minutes. We did not observe any evidence of platelet dysfunction or an increase in surgical bleeding after administration of inhaled epoprostenol.

Recombinant human erythropoietin use in intensive care.

OBJECTIVE: To review the literature concerning the role of recombinant human erythropoietin (rHuEPO) in reducing the need for transfusion in critically ill patients. DATA SOURCES: Articles were obtained through searches of the MEDLINE database (from 1990 to June 2001) using the key words erythropoietin, epoetin alfa, anemia, reticulocytes, hemoglobin, critical care, intensive care, critical illness, and blood transfusion. Additional references were found in the bibliographies of the articles cited. The Cochrane library was also consulted. STUDY SELECTION AND DATA EXTRACTION: Controlled, prospective, and randomized studies on the use of rHuEPO in critically ill adults were selected. DATA SYNTHESIS: Anemia is a common complication in patients requiring intensive care. It is caused, in part, by abnormally low concentrations of endogenous erythropoietin and is mainly seen in patients with sepsis and multiple organ dysfunction syndrome, in whom inflammation mediator concentrations are often elevated. High doses of rHuEPO produce a rapid response in these patients, despite elevated cytokine concentrations. There have been 3 studies on rHuEPO administration in intensive care and 1 trial in acutely burned patients. Only 2 of these studies looked at the impact of rHuEPO administration on the need for transfusion. CONCLUSIONS: Few randomized, controlled trials explore the role of rHuEPO in critical care. Only 1 was a large, randomized clinical trial, but it presents many limitations. Future outcome and safety studies comparing rHuEPO with placebo must include clinical endpoints such as end-organ morbidity, mortality, transfusion criteria, and pharmacoeconomic analysis. rHuEPO appears to provide an erythropoietic response. Optimal dosage and the real impact of rHuEPO on the need for transfusion in intensive care remain to be determined. Currently, based on the evidence available from the literature, rHuEPO cannot be recommended to reduce the need for red blood cell transfusions in anemic, critically ill patients.