Krishna K. Varadhan

The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials.

BACKGROUND & AIMS The aim of the Enhanced Recovery After Surgery (ERAS) pathway is to attenuate the stress response to surgery and enable rapid recovery. The objective of this meta-analysis was to study the differences in outcomes in patients undergoing major elective open colorectal surgery within an ERAS pathway and those treated with conventional perioperative care. METHODS Medline, Embase and Cochrane database searches were performed for relevant studies published between January 1966 and November 2009. All randomized controlled trials comparing ERAS with conventional perioperative care were selected. The outcome measures studied were length of hospital stay, complication rates, readmission rates and mortality. RESULTS Six randomized controlled trials with 452 patients were included. The number of individual ERAS elements used ranged from 4 to 12, with a mean of 9. The length of hospital stay [weighted mean difference (95% confidence interval): -2.55 (-3.24, -1.85)] and complication rates [relative risk (95% confidence interval): 0.53 (0.44, 0.64)] were significantly reduced in the enhanced recovery group. There was no statistically significant difference in readmission and mortality rates. CONCLUSION ERAS pathways appear to reduce the length of stay and complication rates after major elective open colorectal surgery without compromising patient safety.

Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials

Objective To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. Design Meta-analysis of randomised controlled trials. Population Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. Interventions Antibiotic treatment versus appendicectomy. Outcome measures The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. Results Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I2=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. Conclusion Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis.

A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery

BACKGROUND & AIMS Whilst preoperative carbohydrate treatment (PCT) results in beneficial physiological effects, the effects on postoperative clinical outcomes remain unclear and were studied in this meta-analysis. METHODS Prospective studies that randomised adult non-diabetic patients to either PCT (≥50 g oral carbohydrates 2-4 h pre-anaesthesia) or control (fasted/placebo) were included. The primary outcome was length of hospital stay. Secondary outcomes included development of postoperative insulin resistance, complications, nausea and vomiting. Methodological quality was assessed using GRADEpro® software. RESULTS Twenty-one randomised studies of 1685 patients (733 PCT: 952 control) were included. No overall difference in length of stay was noted for analysis of all studies or subgroups of patients undergoing surgery with an expected hospital stay ≤2 days or orthopaedic procedures. However, patients undergoing major abdominal surgery following PCT had reduced length of stay [mean difference, 95% confidence interval: -1.08 (-1.87 to -0.29); I² = 60%, p = 0.007]. PCT reduced postoperative insulin resistance with no effects on in-hospital complications over control (risk ratio, 95% confidence interval, 0.88 (0.50-1.53), I² = 41%; p = 0.640). There was significant heterogeneity amongst studies and, therefore, quality of evidence was low to moderate. CONCLUSIONS PCT may be associated with reduced length of stay in patients undergoing major abdominal surgery, however, the included studies were of low to moderate quality.

A meta-analysis of the effect of combinations of immune modulating nutrients on outcome in patients undergoing major open gastrointestinal surgery

Background:Immune modulating nutrition (IMN) has been shown to reduce complications after major surgery, but strong evidence to recommend its routine use is still lacking. Objective:The aim of this meta-analysis was to evaluate the impact of IMN combinations on postoperative infectious and noninfectious complications, length of hospital stay, and mortality in patients undergoing major open gastrointestinal surgery. Methods:Randomized controlled trials published between January 1980 and February 2011 comparing isocaloric and isonitrogenous enteral IMN combinations with standard diet in patients undergoing major open gastrointestinal surgery were included. The quality of evidence and strength of recommendation for each postoperative outcome were assessed using the GRADE approach and the outcome measures were analyzed with RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark). Results:Twenty-six randomized controlled trials enrolling 2496 patients (1252 IMN and 1244 control) were included. The meta-analysis suggests strong evidence in support of decrease in the incidence of postoperative infectious [risk ratio (RR) (95% confidence interval [CI]): 0.64 (0.55, 0.74)] and length of hospital stay [mean difference (95% CI): −1.88 (−2.91, −0.84 days)] in those receiving IMN. Even though significant benefit was observed for noninfectious complications [RR (95% CI): 0.82 (0.71, 0.95)], the quality of evidence was low. There was no statistically significant benefit on mortality [RR (95% CI): 0.83 (0.49, 1.41)]. Conclusions:IMN is beneficial in reducing postoperative infectious and noninfectious complications and shortening hospital stay in patients undergoing major open gastrointestinal surgery.

Systematic review of the impact of HbA1c on outcomes following surgery in patients with diabetes mellitus

BACKGROUND & AIMS Diabetes is a significant risk factor for surgical complications and also increases the prevalence of comorbidities, thereby increasing surgical risk. The aim of this systematic review was to establish the relationship between long-term preoperative glycemic control as measured by HbA1c and postoperative complications. METHODS A systematic search was conducted to source articles published between 1980 and 2014 pertinent to the review. Full-text articles were included if they met the pre-determined criteria as determined by two reviewers. Studies reporting the impact of preoperative HbA1c levels on postoperative outcomes in all disciplines of surgery were included. RESULTS Twenty studies, including a total of 19,514 patients with diabetes mellitus from a range of surgical specialties, were suitable for inclusion. Preoperative glycemic control did not have a bearing on 30-day mortality. There were no significant differences in the incidence of stroke, venous thromboembolic disease, hospital readmission and ITU length of stay based on glycemic control. The majority of studies suggested no link between preoperative HbA1c levels and acute kidney injury or need for postoperative dialysis, dysrhythmia, infection not related to the surgical site and total hospital length of stay. The literature was highly variable with regards to myocardial events, surgical site infection and reoperation rates. CONCLUSIONS Elevated preoperative HbA1c was not definitively associated with increased postoperative morbidity or mortality in patients with diabetes mellitus. The studies included in this review were relatively heterogeneous, predominantly retrospective, and often contained small patient numbers, suggesting that good quality evidence is necessary.

The effects of resistance exercise training on macro‐ and micro‐circulatory responses to feeding and skeletal muscle protein anabolism in older men

Increases in limb blood flow in response to nutrition are reduced in older age. Muscle microvascular blood flow (MBF) in response to nutrition is also reduced with advancing age and this may contribute to age‐related ‘anabolic resistance’. Resistance exercise training (RET) can rejuvenate limb blood flow responses to nutrition in older individuals. We report here that 20 weeks of RET also restores muscle MBF in older individuals. Restoration of MBF does not, however, enhance muscle anabolic responses to nutrition.

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions

Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 ± 2.1 yr) under postabsorptive and fed [iv Glamin (∼10 g AA), glucose ∼7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-(13)C2]leucine and [(2)H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (+12 ± 5%, P < 0.05), MBV (+25 ± 10%, P < 0.05), and MPS (+129 ± 33%, P < 0.05) increased. Infusion of methacholine further enhanced LBF (+126 ± 12%, P < 0.05) and MBV (+79 ± 30%, P < 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 ± 0.004 vs. 0.08 ± 0.01%/h, P < 0.05) nor improvements in NPB (-4.4 ± 2.4 vs. 16.4 ± 5.7 nmol Phe·100 ml leg(-1)·min(-1), P < 0.05) were affected by methacholine infusion (MPS 0.07 ± 0.01%/h; NPB 24.0 ± 7.7 nmol Phe·100 ml leg(-1)·min(-1)), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism.

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.

Perioperative Fluid Management in Enhanced Recovery

Intravenous fluid therapy is an integral component of perioperative care, but this has, till recently, often been based on little evidence and much dogma, and patients have received either too much or too little fluid. Unfortunately, the morbidity resultant from sub-optimal fluid therapy has often been lost in the seriousness of the conditions (such as sepsis and major trauma) that call for the use of fluids [1]. However, resurgence of interest in perioperative fluid therapy in the twenty-first century has yielded good evidence that optimal fluid management is an important determinant of surgical outcome and that, as far as possible, patients should be managed in a state of zero fluid balance, avoiding both overload and underhydration [2–5].