Sugantha Sundar

Safety and efficacy of corticosteroids for the treatment of septic shock: a systematic review and meta-analysis

BACKGROUND Septic shock is common and results in significant morbidity and mortality. Adjunctive treatment with corticosteroids is common, but definitive data are lacking. We aimed to determine the efficacy and safety of corticosteroid therapy among patients with septic shock. METHODS Medline, Embase, Cochrane Library, Web of Science, and Google Scholar were searched for randomized trials and observational studies published from January 1993 through December 2008. Studies were selected if they included adults with septic shock, discussed treatment with intravenous corticosteroids, and reported at least 1 outcome of interest (e.g., mortality, shock reversal, or incidence of superinfection). Two reviewers independently agreed on eligibility, assessed methodologic quality, and abstracted data. RESULTS Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated for 28-day all-cause mortality, shock reversal at 7 days, and incidence of superinfection with use of random-effects models. Analyses, stratified by adrenal responsiveness, were prespecified. Eight studies (6 randomized trials) involving a total of 1876 patients were selected. Overall, corticosteroid therapy did not result in a statistically significant difference in mortality (42.2% [369 of 875 patients] vs. 38.4% [384 of 1001]; RR, 1.00; 95% CI, 0.84-1.18). A statistically significant difference in the incidence of shock reversal at 7 days was observed between patients who received corticosteroids and those who did not (64.9% [314 of 484 patients] vs. 47.5% [228 of 480]; RR, 1.41; 95% CI, 1.22-1.64), with similar point estimates for both corticotropin stimulation test responders and nonresponders. No statistically significant difference was found in the incidence of superinfection between patients treated with corticosteroids and patients not treated with corticosteroids (25.3% [114 of 450 patients] vs. 22.7% [100 of 441]; RR, 1.11; 95% CI, 0.86-1.42). CONCLUSIONS In patients with septic shock, corticosteroid therapy appears to be safe but does not reduce 28-day all-cause mortality rates. It does, however, significantly reduce the incidence of vasopressor-dependent shock, which may be a clinically worthwhile goal.

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

Background:Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end–expiratory pressure (PEEP) level and occurrence of PPC. Methods:Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. Results:Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose–response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). Conclusions:These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.

BACKGROUND Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING None.

Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis.

Objective:Protective mechanical ventilation with low tidal volumes is standard of care for patients with acute respiratory distress syndrome. The aim of this individual patient data analysis was to determine the association between tidal volume and the occurrence of pulmonary complications in ICU patients without acute respiratory distress syndrome and the association between occurrence of pulmonary complications and outcome in these patients. Design:Individual patient data analysis. Patients:ICU patients not fulfilling the consensus criteria for acute respiratory distress syndrome at the onset of ventilation. Interventions:Mechanical ventilation with low tidal volume. Measurements and Main Results:The primary endpoint was development of a composite of acute respiratory distress syndrome and pneumonia during hospital stay. Based on the tertiles of tidal volume size in the first 2 days of ventilation, patients were assigned to a “low tidal volume group” (tidal volumes⩽ 7 mL/kg predicted body weight), an “intermediate tidal volume group” (> 7 and < 10 mL/kg predicted body weight), and a “high tidal volume group” (≥ 10 mL/kg predicted body weight). Seven investigations (2,184 patients) were included. Acute respiratory distress syndrome or pneumonia occurred in 23% of patients in the low tidal volume group, in 28% of patients in the intermediate tidal volume group, and in 31% of the patients in the high tidal volume group (adjusted odds ratio [low vs high tidal volume group], 0.72; 95% CI, 0.52–0.98; p = 0.042). Occurrence of pulmonary complications was associated with a lower number of ICU-free and hospital-free days and alive at day 28 (10.0 ± 10.9 vs 13.8 ± 11.6 d; p < 0.01 and 6.1 ± 8.1 vs 8.9 ± 9.4 d; p < 0.01) and an increased hospital mortality (49.5% vs 35.6%; p < 0.01). Conclusions:Ventilation with low tidal volumes is associated with a lower risk of development of pulmonary complications in patients without acute respiratory distress syndrome.

Real-time Three-dimensional Echocardiography for Left Atrial Appendage Ligation

A 77-yr-old woman was scheduled to undergo left atrial appendage (LAA) excision and bilateral pulmonary vein isolation through successive right and left mini-thoracotomy incisions for chronic atrial fibrillation. We used a conventional two-dimensional (2D) imaging probe/system (IE-33 Philips Medical Systems, Andover, MA) for a comprehensive transesophageal echocardiographic (TEE) examination and LAA interrogation. Starting from the midesophageal fourchamber plane, the LAA was visualized at 5° increments from 0° to 180° and the presence of spontaneous echo contrast or thrombus was excluded. LAA ejection velocity using pulse wave Doppler in the midesophagus at 0° and 90° rotation was 20 cm/s. Initially, the right-sided pulmonary veins were isolated through a right mini-thoracotomy incision. A left mini-thoracotomy was then performed and LAA excision was performed with a stapling device after left pulmonary venous isolation. Post-LAA excision 2D examination demonstrated a possible “incomplete” excision of the base of the LAA, which appeared as a residual “stump/pouch” of the LAA (Fig. 1) (Video 1; please see video clips available at www.anesthesia-analgesia.org). Because of limited TEE windows secondary to right lateral decubitus position and the small size of the pouch, definite flow could not be demonstrated using color flow Doppler (CFD) despite decreasing the Nyquist limit to 25 cm/s. To confirm our diagnosis of incomplete excision, we decided to use the real-time threedimensional (RT3D) TEE imaging probe on the same system for LAA visualization. Specifically, we used the “3D zoom” mode, which enables live 3D imaging of the intracardiac structures. An en-face view of the staple suture line from within the left atrium (LA) was obtained (Video 1). We were able to appreciate a small residual pouch. This residual LAA was then reexcised with simultaneous visualization with the “live” RT3D system. Positioning and placement of the stapling device was adjusted with simultaneous observation of disappearance of the pouch on the RT3D image. We then observed in “real-time” the application of the staples on the residual defect and its disappearance. Complete excision of the residual stump was also confirmed as absence of the previously visualized defect at the base of the LAA on 2D image as well (Video 1).

Intraoperative Assessment of Perivalvular Mitral Regurgitation: Utility of Three-Dimensional Echocardiography

A M E m c HE APPLICATION OF transesophageal echocardiography (TEE) for the assessment of prosthetic valve function is onsidered a category II indication.1 Although direct surgical xamination of the prosthetic mitral valve is considered the gold standard,” TEE provides a “dynamic” assessment of the alve under varying loading conditions.2 Three-dimensional 3D) TEE imaging may provide additional information to imrove the description of prosthetic valve function and the ocation of perivalvular leaks. The incorporation of color-flow oppler information in the 3D image may also help visualize he complex and eccentric mitral regurgitation (MR) jets. The vailability of this vital information in a timely fashion can help mprove the quality of intraoperative valve assessment. Conventional 2-dimensional (2D) transesophageal echocariography (TEE) is widely used intraoperatively in mitral valve urgery during both valve repair and valve replacement proceures.3 The identification of prosthetic mitral valve dysfunction n the immediate post–cardiopulmonary bypass (CPB) period an provide useful information as to the need for immediate orrective surgery. Previous application of 3D TEE for the ssessment of prosthetic valves in the immediate post-CPB eriod was hampered by the time necessary to acquire and econstruct the 3D volume sets. With the advent of faster econstructive software and hardware, intraoperative 3D echoardiography may provide additional information and improve patial orientation and communication regarding prosthetic alve regurgitation.4 This case report describes a clinical sceario in which the use of 3D echocardiographic reconstruction nd analysis during the post-CPB assessment facilitated idenification and location of a perivalvular leak misidentified with D imaging.

Transesophageal echocardiography in pediatric surgery.

Transesophageal echocardiography (TEE) technology has progressed to the point where small probes are available for intraoperative use in neonates and infants. The most commonly used probes are a biplane probe with 64 elements in each transducer and an output frequency of 5.5 or 7.5 MHz and a 48 element multiplane probe with frequency agility between 4 and 7 MHz. The biplane probe has tip dimensions of 9.1 8.8 mm whereas the multiplane probe has tip dimensions of 10.7 8.0 mm. These TEE probes have been used safely and effectively in low-birth weight infants weighing as little as 1.4 kg. These probes possess continuous wave (CW) Doppler, pulse wave (PW) Doppler, color Doppler, and M-mode capability. Although this technology is capable of providing a wealth of information it should be pointed out that it is not a substitute for comprehensive surgical assessment as there exists a small but definable incidence of both functional and structural discrepancies between TEE and operative findings.

Real-time three-dimensional transesophageal echocardiography and a congenital bilobar left atrial appendage.

Fig 1. (A) The 2D midesophageal view of the LAA showing SEC. The arrow points to the echo density that is questionable for thrombus. (B) Pulsed-wave Doppler of the LAA showing a velocity <20 cm/s

Interaction between peri-operative blood transfusion, tidal volume, airway pressure and postoperative ARDS: an individual patient data meta-analysis

Background Transfusion of blood products and mechanical ventilation with injurious settings are considered risk factors for postoperative lung injury in surgical Patients. Methods A systematic review and individual patient data meta-analysis was done to determine the independent effects of peri-operative transfusion of blood products, intra-operative tidal volume and airway pressure in adult patients undergoing mechanical ventilation for general surgery, as well as their interactions on the occurrence of postoperative acute respiratory distress syndrome (ARDS). Observational studies and randomized trials were identified by a systematic search of MEDLINE, CINAHL, Web of Science, and CENTRAL and screened for inclusion into a meta-analysis. Individual patient data were obtained from the corresponding authors. Patients were stratified according to whether they received transfusion in the peri-operative period [red blood cell concentrates (RBC) and/or fresh frozen plasma (FFP)], tidal volume size [≤7 mL/kg predicted body weight (PBW), 7-10 and >10 mL/kg PBW] and airway pressure level used during surgery (≤15, 15-20 and >20 cmH2O). The primary outcome was development of postoperative ARDS. Results Seventeen investigations were included (3,659 patients). Postoperative ARDS occurred in 40 (7.2%) patients who received at least one blood product compared to 40 patients (2.5%) who did not [adjusted hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.25-4.33; P=0.008]. Incidence of postoperative ARDS was highest in patients ventilated with tidal volumes of >10 mL/kg PBW and having airway pressures of >20 cmH2O receiving both RBC and FFP, and lowest in patients ventilated with tidal volume of ≤7 mL/kg PBW and having airway pressures of ≤15 cmH2O with no transfusion. There was a significant interaction between transfusion and airway pressure level (P=0.002) on the risk of postoperative ARDS. Conclusions Peri-operative transfusion of blood products is associated with an increased risk of postoperative ARDS, which seems more dependent on airway pressure than tidal volume size.