Daniel R. Brown

Intraoperative Tidal Volume as a Risk Factor for Respiratory Failure after Pneumonectomy

Background:Respiratory failure is a leading cause of postoperative morbidity and mortality in patients undergoing pneumonectomy. The authors hypothesized that intraoperative mechanical ventilation with large tidal volumes (VTs) would be associated with increased risk of postpneumonectomy respiratory failure. Methods:Patients undergoing elective pneumonectomy at the authors’ institution from January 1999 to January 2003 were studied. The authors collected data on demographics, relevant comorbidities, neoadjuvant therapy, pulmonary function tests, site and type of operation, duration of surgery, intraoperative ventilator settings, and intraoperative fluid administration. The primary outcome measure was postoperative respiratory failure, defined as the need for continuation of mechanical ventilation for greater than 48 h postoperatively or the need for reinstitution of mechanical ventilation after extubation. Results:Of 170 pneumonectomy patients who met inclusion criteria, 30 (18%) developed postoperative respiratory failure. Causes of postoperative respiratory failure were acute lung injury in 50% (n = 15), cardiogenic pulmonary edema in 17% (n = 5), pneumonia in 23% (n = 7), bronchopleural fistula in 7% (n = 2), and pulmonary thromboembolism in 3% (n = 1). Patients who developed respiratory failure were ventilated with larger intraoperative VT than those who did not (median, 8.3 vs. 6.7 ml/kg predicted body weight; P < 0.001). In a multivariate regression analysis, larger intraoperative VT (odds ratio, 1.56 for each ml/kg increase; 95% confidence interval, 1.12–2.23) was associated with development of postoperative respiratory failure. The interaction between larger VT and fluid administration was also statistically significant (odds ratio, 1.36; 95% confidence interval, 1.05–1.97). Conclusion:Mechanical ventilation with large intraoperative VT is associated with increased risk of postpneumonectomy respiratory failure.

Intraoperative ventilator settings and acute lung injury after elective surgery: a nested case control study

Background: While acute lung injury (ALI) is among the most serious postoperative pulmonary complications, its incidence, risk factors and outcome have not been prospectively studied. Objective: To determine the incidence and survival of ALI associated postoperative respiratory failure and its association with intraoperative ventilator settings, specifically tidal volume. Design: Prospective, nested, case control study. Setting: Single tertiary referral centre. Patients: 4420 consecutive patients without ALI undergoing high risk elective surgeries for postoperative pulmonary complications. Measurements: Incidence of ALI, survival and 2:1 matched case control comparison of intraoperative exposures. Results: 238 (5.4%) patients developed postoperative respiratory failure. Causes included ALI in 83 (35%), hydrostatic pulmonary oedema in 74 (31%), shock in 27 (11.3%), pneumonia in nine (4%), carbon dioxide retention in eight (3.4%) and miscellaneous in 37 (15%). Compared with match controls (n = 166), ALI cases had lower 60 day and 1 year survival (99% vs 73% and 92% vs 56%; p<0.001). Cases were more likely to have a history of smoking, chronic obstructive pulmonary disease and diabetes, and to be exposed to longer duration of surgery, intraoperative hypotension and larger amount of fluid and transfusions. After adjustment for non-ventilator parameters, mean first hour peak airway pressure (OR 1.07; 95% CI 1.02 to 1.15 cm H2O) but not tidal volume (OR 1.03; 95% CI 0.84 to 1.26 ml/kg), positive end expiratory pressure (OR 0.89; 95% CI 0.77 to 1.04 cm H2O) or fraction of inspired oxygen (OR 1.0; 95% CI 0.98 to 1.03) were associated with ALI. Conclusion: ALI is the most common cause of postoperative respiratory failure and is associated with markedly lower postoperative survival. Intraoperative tidal volume was not associated with an increased risk for early postoperative ALI.

Effect of leptin deficiency on metabolic rate in ob/ob mice

Reduced metabolic rate may contribute to weight gain in leptin-deficient ( ob/ob) mice; however, available studies have been criticized for referencing O2 consumption (V˙o 2) to estimated rather than true lean body mass. To evaluate whether leptin deficiency reduces energy expenditure, four separate experiments were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass, permittingV˙o 2 to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to eliminate differences in body weight and composition between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3 mg ⋅ kg-1 ⋅ day-1) on V˙o 2 were examined; and 4) body weight and composition were compared in leptin-repleted and pair-fed ob/ob animals. ob/ob animals had greater mass, less lean body mass, and a 10% higher metabolic rate whenV˙o 2 was referenced to lean mass. Dietary manipulation achieved identical body weight in ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin increasedV˙o 2 in ob/ob but not control animals. Weight loss in leptin-repleted ob/ob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observed increase inV˙o 2 and accelerated weight loss seen with leptin repletion, that leptin deficiency causes a reduction in metabolic rate in ob/obmice. In contrast, these physiological studies suggest that comparison of V˙o 2 in obese and lean animals does not produce useful information on the contribution of leptin to metabolism.Reduced metabolic rate may contribute to weight gain in leptin-deficient (ob/ob) mice; however, available studies have been criticized for referencing O2 consumption (VO2) to estimated rather than true lean body mass. To evaluate whether leptin deficiency reduces energy expenditure, four separate experiments were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass, permitting VO2 to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to eliminate differences in body weight and composition between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3 mg. kg-1. day-1) on VO2 were examined; and 4) body weight and composition were compared in leptin-repleted and pair-fed ob/ob animals. ob/ob animals had greater mass, less lean body mass, and a 10% higher metabolic rate when VO2 was referenced to lean mass. Dietary manipulation achieved identical body weight in ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin increased VO2 in ob/ob but not control animals. Weight loss in leptin-repleted ob/ob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observed increase in VO2 and accelerated weight loss seen with leptin repletion, that leptin deficiency causes a reduction in metabolic rate in ob/ob mice. In contrast, these physiological studies suggest that comparison of VO2 in obese and lean animals does not produce useful information on the contribution of leptin to metabolism.

Clinical Spectrum, Frequency, and Significance of Myocardial Dysfunction in Severe Sepsis and Septic Shock

OBJECTIVE To determine the frequency and spectrum of myocardial dysfunction in patients with severe sepsis and septic shock using transthoracic echocardiography and to evaluate the impact of the myocardial dysfunction types on mortality. PATIENTS AND METHODS A prospective study of 106 patients with severe sepsis or septic shock was conducted from August 1, 2007, to January 31, 2009. All patients underwent transthoracic echocardiography within 24 hours of admission to the intensive care unit. Myocardial dysfunction was classified as left ventricular (LV) diastolic, LV systolic, and right ventricular (RV) dysfunction. Frequency of myocardial dysfunction was calculated, and demographic, hemodynamic, and physiologic variables and mortality were compared between the myocardial dysfunction types and patients without cardiac dysfunction. RESULTS The frequency of myocardial dysfunction in patients with severe sepsis or septic shock was 64% (n=68). Left ventricular diastolic dysfunction was present in 39 patients (37%), LV systolic dysfunction in 29 (27%), and RV dysfunction in 33 (31%). There was significant overlap. The 30-day and 1-year mortality rates were 36% and 57%, respectively. There was no difference in mortality between patients with normal myocardial function and those with left, right, or any ventricular dysfunction. CONCLUSION Myocardial dysfunction is frequent in patients with severe sepsis or septic shock and has a wide spectrum including LV diastolic, LV systolic, and RV dysfunction types. Although evaluation for the presence and type of myocardial dysfunction is important for tailoring specific therapy, its presence in patients with severe sepsis and septic shock was not associated with increased 30-day or 1-year mortality.

Analytic Reviews: Propofol Infusion Syndrome in the ICU

Propofol is an alkylphenol derivative named 2, 6, diisopropylphenol and is a potent intravenous short-acting hypnotic agent. It is commonly used as sedation, as well as an anesthetic agent in both pediatric and adult patient populations. There have been numerous case reports describing a constellation of findings including metabolic derangements and organ system failures known collectively as propofol infusion syndrome (PRIS). Although there is a high mortality associated with PRIS, the precise mechanism of action has yet to be determined. The best preventive measure for this syndrome is awareness and avoidance of clinical scenarios associated with development of PRIS. There is no established treatment for PRIS; care is primarily supportive in nature and may include the full array of advanced cardiopulmonary support, including extracorporeal membrane oxygenation (ECMO). This article reviews the reported cases of PRIS and describes the current understanding of the underlying pathophysiology and treatment options.

Rapid-Sequence Intubation A Review of the Process and Considerations When Choosing Medications

Objective: To summarize published data regarding the steps of rapid-sequence intubation (RSI); review premedications, induction agents, neuromuscular blockers (NMB), and studies supporting use or avoidance; and discuss the benefits and deficits of combinations of induction agents and NMBs used when drug shortages occur. Data Source: A search of Medline databases (1966–October 2013) was conducted. Study Selection and Data Extraction: Databases were searched using the terms rapid-sequence intubation, fentanyl, midazolam, atropine, lidocaine, phenylephrine, ketamine, propofol, etomidate thiopental, succinylcholine, vecuronium, atracurium, and rocuronium. Citations from publications were reviewed for additional references. Data Synthesis: Data were reviewed to support the use or avoidance of premedications, induction agents, and paralytics and combinations to consider when drug shortages occur. Conclusions: RSI is used to secure a definitive airway in often uncooperative, nonfasted, unstable, and/or critically ill patients. Choosing the appropriate premedication, induction drug, and paralytic will maximize the success of tracheal intubation and minimize complications.

Intrathecal anesthesia and recovery from radical prostatectomy: a prospective, randomized, controlled trial.

BackgroundPrevious studies suggest that intraoperative anesthetic care may influence postoperative pain and recovery from surgery. The authors tested the hypothesis that the addition of intrathecal analgesia to general anesthesia would improve long-term functional status and decrease pain in patients undergoing radical retropubic prostatectomy. MethodsOne hundred patients received either general anesthesia supplemented with intravenous fentanyl or general anesthesia preceded by intrathecal administration of bupivacaine (15 mg), clonidine (75 &mgr;g), and morphine (0.2 mg). Patients and providers were masked to treatment assignment. All patients received multimodal pain management postoperatively. Primary outcomes included pain and functional status over the first 12 postoperative weeks. ResultsPatients receiving intrathecal analgesia required more intravenous fluids and vasopressors intraoperatively. Pain was well controlled throughout the study (mean numerical pain scores < 3 in both groups at all times studied). Intrathecal analgesia decreased pain and supplemental intravenous morphine use over the first postoperative day but increased the frequency of pruritus. Pain and functional status after discharge from the hospital did not differ between groups. Intrathecal analgesia significantly decreased the duration of hospital stay (from 2.8 ± 2.0 to 2.1 ± 0.5 days; P < 0.01) as a result of five patients in the control group who stayed in the hospital more than 3 days. ConclusionsThe benefits of improved immediate analgesia and decreased morphine requirements resulting from intrathecal analgesia must be weighed against factors such as pruritus, increased intraoperative requirement for fluids and vasopressors, and resources needed to implement this modality. Further studies are needed to determine the significance of the decrease in duration of hospital stay.

A prospective trial of elective extubation in brain injured patients meeting extubation criteria for ventilatory support: A feasibility study

IntroductionTo assess the safety and feasibility of recruiting mechanically ventilated patients with brain injury who are solely intubated for airway protection and randomising them into early or delayed extubation, and to obtain estimates to refine sample-size calculations for a larger study. The design is a single-blinded block randomised controlled trial. A single large academic medical centre is the setting.MethodsSixteen neurologically stable but severely brain injured patients with a Glasgow Coma Score (GCS) of 8 or less were randomised to early or delayed extubation until their neurological examination improved. Eligible patients met standard respiratory criteria for extubation and passed a modified Airway Care Score (ACS) to ensure adequate control of respiratory secretions. The primary outcome measured between groups was the functional status of the patient at hospital discharge as measured by a Modified Rankin Score (MRS) and Functional Independence Measure (FIM). Secondary measurements included the number of nosocomial pneumonias and re-intubations, and intensive care unit (ICU) and hospital length of stay. Standard statistical assessments were employed for analysis.ResultsFive female and eleven male patients ranging in age from 30 to 93 years were enrolled. Aetiologies responsible for the neurological injury included six head traumas, three brain tumours, two intracerebral haemorrhages, two subarachnoid haemorrhages and three ischaemic strokes. There were no demographic differences between the groups. There were no unexpected deaths and no significant differences in secondary measures. The difference in means between the MRS and FIM were small (0.25 and 5.62, respectively). These results suggest that between 64 and 110 patients are needed in each treatment arm to detect a treatment effect with 80% power.ConclusionsRecruitment and randomisation of severely brain injured patients appears to be safe and feasible. A large multicentre trial will be needed to determine if stable, severely brain injured patients who meet respiratory and airway control criteria for extubation need to remain intubated.

The impact of rapid response team on outcome of patients transferred from the ward to the ICU: a single-center study.

Objectives:To determine the impact of rapid response team implementation on the outcome of patients transferred from the regular hospital ward and nonward locations to the ICU. Design:Retrospective before–after cohort study. Setting:The study was performed in two ICUs, one surgical and one medical, of a tertiary medical center. Patients:We included 4,890 patients transferred from the hospital ward to two ICUs and 15,855 patients admitted from nonward locations. Interventions:None. Measurements and Main Results:Data on each patient were abstracted from the Acute Physiology and Chronic Health Evaluation III and the administrative hospital and rapid response team databases. The study period was divided into pre–rapid response team and rapid response team. A 24/7 critical care consult service and cardiac arrest teams were available for ward patient care during both periods. A total of 20,745 patients were admitted to the two study ICUs, of whom 4,890 were from the ward (2,466 and 2,424 during the pre–rapid response team and rapid response team periods, respectively). The first ICU day severity of illness was higher for the pre–rapid response team period. A multiple logistic regression model that included predicted mortality as a covariate suggested that availability of rapid response team was associated with an increased risk of hospital death in patients transferred to the ICU from the regular ward, odds ratio (95% CI) of 1.273 (1.089–1.490). For the nonward patients, the availability of rapid response team was similarly associated with increased risk of death. The ICU length of stay was shorter during the rapid response team period both in ward transfer and in nonward transfer patients. Conclusions:Rapid response team implementation is associated with increased numbers of ICU admissions and rates, and transfer from the ward of less severely ill patients. However, rapid response team implementation did not improve the severity-of-illness-adjusted outcome of patients transferred from the ward. Implementation of rapid response team in an institution with a 24/7 ICU consult service may have unforeseen costs without obvious benefit. Our findings highlight that institutions should evaluate the impact of rapid response team on patient outcome and make modifications specific to their practices.

Perioperative Statin Therapy and Renal Outcomes After Major Vascular Surgery: A Propensity-Based Analysis

OBJECTIVE To evaluate how the presence and timing of statin therapy affect perioperative renal outcomes after major vascular surgery. DESIGN Retrospective cohort study. SETTING Surgical intensive care unit at a single academic medical center. PARTICIPANTS Patients undergoing major vascular surgery between July 2004 and October 2005. MEASUREMENTS AND MAIN RESULTS The presence and timing of perioperative statin administration and the propensity for receiving such therapy were noted. Renal outcomes, lengths of stay, and mortality were reviewed. One hundred fifty-one procedures were performed. Eighty-nine patients (59%) received statin therapy. There was no evidence for renal protection with perioperative statin therapy (Delta creatinine 0.2 mg/dL v 0.2 mg/dL, p = 0.41; acute renal injury/acute renal failure 8% v 6%, p = 1.00; renal replacement therapy 3% v 3%, p = 1.00; all statin v no statin, respectively). With the possible exception of early reinstitution of statin therapy in chronic statin users, subgroup analyses failed to confirm an association between statin timing and prevention of postoperative renal dysfunction. CONCLUSIONS In the present investigation, neither the presence nor timing of perioperative statin therapy was associated with improved renal outcomes in patients undergoing a range of major vascular procedures. A possible exception is early postoperative reinitiation of statin therapy in chronic statin users. The discrepant results of available literature preclude a definitive statement on the use of statin therapy as a means of preventing postoperative renal dysfunction. An adequately powered prospective trial is needed before advocating the routine use of statin therapy for perioperative renal protection.