Clonidine Does Not Reduce Pain or Opioid Consumption After Noncardiac Surgery.

BACKGROUND: Clonidine is an α2-adrenoceptor agonist, which has analgesic properties. However, the analgesic efficacy of perioperative clonidine remains unclear. We, therefore, tested the hypothesis that clonidine reduces both pain scores and cumulative opioid consumption during the initial 72 hours after noncardiac surgery. METHODS: Six hundred twenty-four patients undergoing elective noncardiac surgery under general and spinal anesthesia were included in this substudy of the PeriOperative ISchemia Evaluation-2 trial. Patients were randomly assigned to 0.2 mg oral clonidine or placebo 2 to 4 hours before surgery, followed by 0.2 mg/d transdermal clonidine patch or placebo patch, which was maintained until 72 hours after surgery. Postoperative pain scores and opioid consumption were assessed for 72 hours after surgery. RESULTS: Clonidine had no effect on opioid consumption compared with placebo, with an estimated ratio of means of 0.98 (95% confidence interval, 0.70-1.38); P = 0.92. Median (Q1, Q3) opioid consumption was 63 (30, 154) mg morphine equivalents in the clonidine group, which was similar to 60 (30, 128) mg morphine equivalents in the placebo group. Furthermore, there was no significant effect on pain scores, with an estimated difference in means of 0.12 (95% confidence interval, -0.02 to 0.26); 11-point scale; P = 0.10. Mean pain scores per patient were 3.6 ± 1.8 for clonidine patients and 3.6 ± 1.8 for placebo patients. CONCLUSIONS: Clonidine does not reduce opioid consumption or pain scores in patients recovering from noncardiac surgery.

ß-Blockers in sepsis: protocol for a systematic review and meta-analysis of randomised control trials.

INTRODUCTION: Sepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of ß-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of ß-blockers in adults with sepsis using data from randomised control trials. METHODS AND ANALYSIS: We will identify randomised control trials comparing treatment with ß-blockers, versus placebo or standard care in adults with sepsis. Data sources will include MEDLINE, EMBASE, CENTRAL, clinical trial registries and conference proceedings. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, risk of bias assessment and evaluation of the quality of the evidence using the GRADE approach. ETHICS AND DISSEMINATION: Our systematic review will evaluate the effects of ß-blockers in adults with sepsis, comprehensively summarising and appraising the available evidence from randomised control trials. The results of this systematic review will help clinicians treating patients with sepsis to understand the potential role of ß-blockade, and inform future research on this topic. Our findings will be disseminated through conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42016036933.

Kidney Function Alters the Relationship between Postoperative Troponin T Level and Death.

Cardiac troponin T (cTnT), even at low concentrations, is a risk factor for 30-day mortality in patients undergoing noncardiac surgery, but it is uncertain whether that risk is generalizable to patients with poor kidney function. We, therefore, evaluated the relationship between cTnT concentration and kidney function on the outcome of 30-day mortality in a post hoc analysis of a prospective cohort study of patients undergoing noncardiac surgery. cTnT was measured for 3 days after surgery and considered abnormal if the peak was ≥0.02 ng/ml. Of the included 14,037 patients, 267 (1.9%) patients died within 30 days of surgery. The adjusted hazard ratios for death with an abnormal cTnT concentration were 4.37 (95% confidence intervals [95% CI], 3.21 to 6.22), 6.15 (95% CI, 2.95 to 140.9), 6.30 (95% CI, 3.12 to 21.23), 1.33 (95% CI, 0.56 to 4.85), and 1.46 (95% CI, 0.46 to 9.21) for eGFR≥60, 45 to <60, 30 to <45, 15 to <30, and <15 ml/min per 1.73 m(2) or on dialysis, respectively. Compared with patients with eGFR≥60 ml/min per 1.73 m(2), the adjusted hazard ratio was significantly lower for patients with eGFR=15 to <30 ml/min per 1.73 m(2) (interaction P value=0.02). Redefining abnormal cTnT concentration as ≥0.03 ng/ml or a change of ≥0.02 ng/ml did not alter results. Because the risk associated with postoperative cTnT levels may be different for patients with eGFR<30 ml/min per 1.73 m(2), additional research is required to determine how to interpret perioperative cTnT values for patients with low kidney function.

Statin use associates with a lower incidence of acute kidney injury after major elective surgery.

Statins abrogate ischemic renal injury in animal studies but whether they are renoprotective in humans is unknown. We conducted a population-based retrospective cohort study that included 213,347 older patients who underwent major elective surgery in the province of Ontario, Canada from 1995 to 2008. During the first 14 postoperative days, 1.9% (4020 patients), developed acute kidney injury and 0.5% (1173 patients), required acute dialysis. The 30-day mortality rate was 2.8% (5974 patients). Prior to surgery, 32% of patients were taking a statin. After statistical adjustment for patient and surgical characteristics, statin use associated with 16% lower odds of acute kidney injury (OR, 0.84; 95% CI, 0.79 to 0.90), 17% lower odds of acute dialysis (OR, 0.83; 95% CI, 0.72 to 0.95), and 21% lower odds of mortality (OR, 0.79; 95% CI, 0.74 to 0.85). Propensity score matching produced similar results. These data suggest that statins may protect against renal complications after major elective surgery and reduce perioperative mortality.

Deep venous thrombosis: clinically silent in the intensive care unit.

PURPOSE: The reliability of clinical signs and the physical examination in the evaluation of deep venous thrombosis (DVT) in the critically ill is unknown. The purpose of this study was to determine the diagnostic properties of clinical examination for signs of DVT in a cohort of medical-surgical intensive care unit (ICU) patients using screening compression ultrasonography as a reference standard. MATERIALS AND METHODS: We prospectively included patients older than 18 years with an expected length of ICU stay of more than 72 hours. Patients underwent bilateral lower limb screening compression ultrasound twice weekly and structured physical examination twice weekly by 2 independent trained research coordinators blinded to the ultrasonography results. We classified patients according to 2 methods: method 1, a DVT Risk Stratification System of 3 categories and method 2, a DVT Risk Score, both of which use the history and physical examination to stratify patients for their risk of DVT. RESULTS: We included 239 patients in our study, 32 of whom had DVT based on the results of their compression ultrasound. We excluded 7 patients with DVT on ICU admission and 2 who did not undergo any structured examinations. We matched controls with cases (9:1) based on duration of ICU stay. Cases and controls were then allocated to low, moderate, and high risk strata for DVT. Using method 1, the area under the receiver operating characteristic curve (AUC) was 0.57 (95% CI, 0.33-0.78, P = .01). Using method 2, the AUC was 0.59 (95% CI, 0.42-0.75, P = .02). An AUC of 1.0 indicates an ideal test, and AUC of 0.50 indicates a test with no diagnostic utility. CONCLUSIONS: The history and physical examination for DVT are not useful in detecting lower limb DVT in the ICU.