Peter Rock

Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury

CONTEXT The omega-3 (n-3) fatty acids docosahexaenoic acid and eicosapentaenoic acid, along with γ-linolenic acid and antioxidants, may modulate systemic inflammatory response and improve oxygenation and outcomes in patients with acute lung injury. OBJECTIVE To determine if dietary supplementation of these substances to patients with acute lung injury would increase ventilator-free days to study day 28. DESIGN, SETTING, AND PARTICIPANTS The OMEGA study, a randomized, double-blind, placebo-controlled, multicenter trial conducted from January 2, 2008, through February 21, 2009. Participants were 272 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. All participants had complete follow-up. INTERVENTIONS Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants compared with an isocaloric control. Enteral nutrition, directed by a protocol, was delivered separately from the study supplement. MAIN OUTCOME MEASURE Ventilator-free days to study day 28. RESULTS The study was stopped early for futility after 143 and 129 patients were enrolled in the n-3 and control groups. Despite an 8-fold increase in plasma eicosapentaenoic acid levels, patients receiving the n-3 supplement had fewer ventilator-free days (14.0 vs 17.2; P = .02) (difference, -3.2 [95% CI, -5.8 to -0.7]) and intensive care unit-free days (14.0 vs 16.7; P = .04). Patients in the n-3 group also had fewer nonpulmonary organ failure-free days (12.3 vs 15.5; P = .02). Sixty-day hospital mortality was 26.6% in the n-3 group vs 16.3% in the control group (P = .054), and adjusted 60-day mortality was 25.1% and 17.6% in the n-3 and control groups, respectively (P = .11). Use of the n-3 supplement resulted in more days with diarrhea (29% vs 21%; P = .001). CONCLUSIONS Twice-daily enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants did not improve the primary end point of ventilator-free days or other clinical outcomes in patients with acute lung injury and may be harmful. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00609180.

Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome

BACKGROUND In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. RESULTS The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).

Acute Kidney Injury in Patients with Acute Lung Injury: Impact of Fluid Accumulation on Classification of Acute Kidney Injury and Associated Outcomes

Objective:It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality. Design:Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter. Setting:Acute Respiratory Distress Syndrome Network hospitals. Patients:One thousand patients. Interventions:None. Measurements and Main Results:The incidence of acute kidney injury, defined as an absolute rise in creatinine of ≥0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18). Conclusions:Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with “unrecognized” acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.

Perioperative Management of Adult Surgical Patients on Extracorporeal Membrane Oxygenation Support

XTRACORPOREAL MECHANICAL support devices are used as an adjunct in the management of critically ill patients who are refractory to more conventional modes of therapy. Extracorporeal membrane oxygenation (ECMO) is one such device that has been used mainly in the management of patients in cardiogenic shock or respiratory failure who failed therapy on maximal ventilator settings and maximal pharmacologic support. ECMO has the advantage of being rapidly deployable, both at the bedside and in the operating room, and can be initiated without the need for general anesthesia. ECMO has been used as a bridging device to recovery or to more definitive therapy. In patients who are awaiting lung transplantation, ECMO has been used as a bridge to transplant when decompensation occurs and also as an adjunct in physical rehabilitation before transplant. The science and instrumentation of ECMO are direct outgrowths of the development of cardiopulmonary bypass (CPB) technology that reached its full potential in support of cardiac surgery in the latter half of the 20th century. This is a fascinating history in itself and has been reviewed thoughtfully at key points by physician-scientists directly involved in the process. 1-3 Over the last decade, the design and reliability of components of the ECMO circuit have improved markedly from earlier iterations, and clinical teams have gained experience with a multidisciplinary approach to the management of patients on ECMO. These advancements have led to more prolonged and widespread use of ECMO as an alternative for support in patients with otherwise nonsurvivable respiratory or cardiopulmonary failure. Outcomes also have improved from what is reported in the older medical literature. With the increase in the use of ECMO, anesthesiologists have become more involved in the perioperative management of these critically ill patients, and an understanding of the physiologic changes that occur in patients on ECMO is essential for perioperative management. In addition, a number of issues remain controversial, mainly regarding risk/benefit differentials in pediatric versus older age groups, end-stage versus acute disease, and the timing and duration of therapy. This review addresses the practical clinical problems during the perioperative management of adult patients on ECMO. TYPES OF ECMO Three major configurations of ECMO are available. Venovenous (VV) ECMO is used in the management of patients with refractory pulmonary failure and stable cardiovascular status. Venoarterial (VA) ECMO is used in patients with refractory cardiogenic shock or cardiorespiratory failure. The third configuration, arteriovenous (AV) ECMO, also known as the “artificial lung,” can be used in patients with acute lung injury presenting with stable cardiovascular status. In this review, the term “inflow cannula” refers to the cannula that carries blood from the patient into the ECMO system, and “outflow cannula” refers to the cannula that carries oxygenated blood from the ECMO system back to the patient. In VV ECMO, the inflow and outflow ECMO cannulae run in and out of the venous system in the patient. In VA ECMO, the inflow cannula is from the patient’s venous system, but the outflow cannula runs into the arterial system. Conversely, in AV ECMO, the inflow cannula is from the patient’s arterial system with the outflow cannula from the oxygenator running into the patient’s venous system. AV ECMO differs from VA and VV ECMO in that the AV ECMO circuit does not incorporate a pump to maintain blood flow in the circuit. Blood flow in this type of circuit is a function of systemic blood pressure, cardiovascular stability, the resistance of the membrane oxygenator, the size and length of the conducting circuit, and blood viscosity. Adequate blood pressure and cardiovascular stability are required to maintain blood flow in this form of circuit. Commonly used inflow cannulation sites during VV and VA ECMO are the femoral vein, the inferior vena cava, the superior vena cava, and the right atrium. Outflow during VV ECMO may be into any of these sites. In patients on VA ECMO, inflow usually is into the femoral artery, axillary artery, ascending aorta, or the pulmonary artery. Inflow during AV ECMO may

Preoperative Aspirin Use and Lung Injury After Aortic Valve Replacement Surgery: A Retrospective Cohort Study.

BACKGROUND:Acute respiratory distress syndrome (ARDS) occurs uncommonly after cardiac surgery but has a mortality rate as high as 80%. Aspirin may prevent lung injury in at-risk patients by reducing platelet-neutrophil aggregates in the lung. We hypothesized that preoperative aspirin use would be associated with a decreased risk of ARDS after aortic valve replacement surgery. METHODS:We performed a retrospective single-center cohort study that included all adult patients who had aortic valve replacement surgery during a 5-year period. The primary outcome variable was postoperative ARDS. The secondary outcome variable was nadir PaO2/FIO2 ratio during the first 72 hours after surgery. Both crude and propensity score–adjusted logistic regression analyses were performed to estimate the odds ratio for developing ARDS in aspirin users. Subgroups were analyzed to determine whether preoperative aspirin use might be associated with improved oxygenation in patients with specific risk factors for lung injury. RESULTS:Of the 375 patients who had aortic valve replacement surgery during the study period, 181 patients took aspirin preoperatively (48.3%) with most taking a dose of 81 mg (72.0%). There were 22 cases of ARDS in the cohort (5.5%). There was no significant difference in the rate of ARDS between aspirin users and nonusers (5.0% vs 6.7%, P = 0.52). There was also no significant difference in the nadir PaO2/FIO2 ratio between aspirin users and nonusers (P = 0.12). The crude odds ratio for ARDS in aspirin users was 0.725 (99% confidence interval, 0.229–2.289; P = 0.47), and the propensity score–adjusted odds ratio was 0.457 (99% confidence interval, 0.120–1.730; P = 0.13). CONCLUSIONS:Within the constraints of this analysis that included only 22 affected patients, preoperative aspirin use was not associated with a decreased incidence of ARDS after aortic valve replacement surgery or improved oxygenation.

Increased ICU resource needs for an academic emergency general surgery service

Objective:ICU needs of nontrauma emergency general surgery patients are poorly described. This study was designed to compare ICU utilization of emergency general surgery patients admitted to an acute care emergency surgery service with other general surgery patients. Our hypothesis is that tertiary care emergency general surgery patients utilize more ICU resources than other general surgical patients. Design:Retrospective database review. Setting:Academic, tertiary care, nontrauma surgical ICU. Patients:All patients admitted to the surgical ICU over age 18 between March 2004 and June 2012. Interventions:None. Measurements and Main Results:Six thousand ninety-eight patients were evaluated: 1,053 acute care emergency surgery, 1,964 general surgery, 1,491 transplant surgery, 995 facial surgery/otolaryngology, and 595 neurosurgery. Acute care emergency surgery patients had statistically significantly longer ICU lengths of stay than other groups: acute care emergency surgery (13.5 ± 17.4 d) versus general surgery (8.7 ± 12.9), transplant (7.8 ± 11.6), oral-maxillofacial surgery (5.5 ± 4.2), and neurosurgery (4.47 ± 9.8) (all p< 0.01). Ventilator usage, defined by percentage of total ICU days patients required mechanical ventilation, was significantly higher for acute care emergency surgery patients: acute care emergency surgery 73.4% versus general surgery 64.9%, transplant 63.3%, oral-maxillofacial surgery 58.4%, and neurosurgery 53.1% (all p < 0.01). Continuous renal replacement therapy usage, defined as percent of patients requiring this service, was significantly higher in acute care emergency surgery patients: acute care emergency surgery 10.8% versus general surgery 4.3%, transplant 6.6%, oral-maxillofacial surgery 0%, and neurosurgery 0.5% (all p < 0.01). Acute care emergency surgery patients were more likely interhospital transfers for tertiary care services than general surgery or transplant (24.5% vs 15.5% and 8.3% respectively, p < 0.001 for each) and more likely required emergent surgery (13.7% vs 6.7% and 3.5%, all p < 0.001). Chronic comorbidities were similar between acute care emergency surgery and general surgery, whereas transplant had fewer. Conclusions:Emergency general surgery patients have increased ICU needs in terms of length of stay, ventilator usage, and continuous renal replacement therapy usage compared with other services, perhaps due to the higher percentage of transfers and emergent surgery required. These patients represent a distinct population. Understanding their resource needs will allow for better deployment of hospital resources.

Past history of skin infection and risk of surgical site infection after elective surgery.

Objective:To identify baseline patient characteristics associated with increased susceptibility to surgical site infection (SSI) after elective surgery. Background:The Center for Medicare and Medicaid Services considers SSI to be preventable through adherence to current infection control practices; however, the etiology of wound infection is incompletely understood. Methods:Prospective cohort study involving patients undergoing cardiac, vascular, craniotomy, and spinal surgery at 2 academic medical centers in Baltimore, MD. A comprehensive medical history was obtained at baseline, and participants were followed for 6 months using active inpatient and outpatient surveillance for deep SSI and infectious death. Infection control best practices were monitored perioperatively. The relative risk of SSI/infectious death was determined comparing those with versus those without a past medical history of skin infection using Cox proportional hazards models. Results:Of 613 patients (mean [SD] = 62.3 [11.5] years; 42.1% women), 22.0% reported a history of skin infection. The cumulative incidence of deep SSI/infectious death was 6.7% versus 3.1% for those with and without a history of skin infection, respectively (unadjusted hazard ratio (HR) = 2.25; 95% confidence interval (95% CI), 0.98–5.14; P = 0.055). Risk estimates increased after adjustments for demographic and socioeconomic variables (HR = 2.82; 95% CI, 1.18–6.74; P = 0.019) and after propensity score adjustment for all potential confounders (HR = 3.41; 95% CI, 1.36–8.59; P = 0.009). Adjustments for intraoperative infection risk factors and adherence to infection control best practice metrics had no impact on risk estimates. Conclusions:A history of skin infection identified a state of enhanced susceptibility to SSI at baseline that is independent of traditional SSI risk factors and adherence to current infection control practices.

Surgical Site Infection after Renal Transplantation

OBJECTIVE To identify factors associated with the development of surgical site infection (SSI) among adult patients undergoing renal transplantation DESIGN A retrospective cohort study. SETTING An urban tertiary care center in Baltimore, Maryland, with a well-established renal transplantation program that performs ~200-250 renal transplant procedures annually. RESULTS At total of 441 adult patients underwent renal transplantation between January 1, 2010, and December 31, 2011. Of these 441 patients, 66 (15%) developed an SSI; of these 66, 31 (47%) were superficial incisional infections and 35 (53%) were deep-incisional or organ-space infections. The average body mass index (BMI) among this patient cohort was 29.7; 84 (42%) were obese (BMI >30). Patients who developed an SSI had a greater mean BMI (31.7 vs 29.4; P=.004) and were more likely to have a history of peripheral vascular disease, rheumatologic disease, and narcotic abuse. History of cerebral vascular disease was protective. Multivariate analysis showed BMI (odds ratio [OR] 1.06; 95% confidence interval [CI], 1.02-1.11) and past history of narcotic use/abuse (OR, 4.86; 95% CI, 1.24-19.12) to be significantly associated with development of SSI after controlling for National Healthcare Surveillance Network (NHSN) score and presence of cerebrovascular, peripheral vascular, and rheumatologic disease. CONCLUSIONS We identified higher BMI as a risk factor for the development of SSI following renal transplantation. Notably, neither aggregate comorbidity scores nor NHSN risk index were associated with SSI in this population. Additional risk adjustment measures and research in this area are needed to compare SSIs across transplant centers.

Upper airway obstruction and infant botulism

he diagnosis of the etiology of acute upper airway obstruction (UAO) presents difficulties T in infants but is important as any coexisting disease may itself be fatal. Guidelines for identifkation and management of UAO have been defined (1-3) and include multispecialty evaluation and carefully controlled operating room care. While urgently addressing a critical airway, the broad differential diagnosis of UAO must be considered (4). We present a case of acute UAO, first thought to be epiglottitis, in a patient who subsequently was found to have infant botulism. This is the first case report of botulism mimicking epiglottitis and causing acute UAO.

Effect of cardiopulmonary bypass on platelet mitochondrial respiration and correlation with aggregation and bleeding: a pilot study

Background: Cardiopulmonary bypass (CPB) may cause platelet dysfunction, contributing to bleeding. There are no investigations of how CPB affects platelet mitochondrial respiration and what correlation this has with platelet aggregation and bleeding. Methods: We studied platelet mitochondrial respiration and aggregation in eighteen adult cardiac surgery patients having CPB. The relationships between respiration, aggregation and postoperative bleeding were analyzed. Results: Platelet respiration, reflected by the respiratory control ratio (RCR), was unchanged after CPB (mean difference in RCR= −0.02 (95% CI=−1.45 to 1.42), p=0.98). Further, there were no significant relationships between indexed adenosine diphosphate (ADP) or thrombin receptor-activating peptide (TRAP)-induced aggregation and the RCR (p=0.12 and p=0.41). Only post-CPB ADP - induced aggregation correlated with 24-hr chest tube output (p=0.04), but indexing for platelet count attenuated the effect (p=0.07). Conclusion: Platelet mitochondrial respiration is preserved after CPB and is not correlated with aggregation or bleeding. Only post-CPB, ADP-induced aggregation correlates with postoperative bleeding.