Christian S. Meyhoff

Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.

CONTEXT Use of 80% oxygen during surgery has been suggested to reduce the risk of surgical wound infections, but this effect has not been consistently identified. The effect of 80% oxygen on pulmonary complications has not been well defined. OBJECTIVE To assess whether use of 80% oxygen reduces the frequency of surgical site infection without increasing the frequency of pulmonary complications in patients undergoing abdominal surgery. DESIGN, SETTING, AND PATIENTS The PROXI trial, a patient- and observer-blinded randomized clinical trial conducted in 14 Danish hospitals between October 2006 and October 2008 among 1400 patients undergoing acute or elective laparotomy. INTERVENTIONS Patients were randomly assigned to receive either 80% or 30% oxygen during and for 2 hours after surgery. MAIN OUTCOME MEASURES Surgical site infection within 14 days, defined according to the Centers for Disease Control and Prevention. Secondary outcomes included atelectasis, pneumonia, respiratory failure, and mortality. RESULTS Surgical site infection occurred in 131 of 685 patients (19.1%) assigned to receive 80% oxygen vs 141 of 701 (20.1%) assigned to receive 30% oxygen (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.72-1.22; P = .64). Atelectasis occurred in 54 of 685 patients (7.9%) assigned to receive 80% oxygen vs 50 of 701 (7.1%) assigned to receive 30% oxygen (OR, 1.11; 95% CI, 0.75-1.66; P = .60), pneumonia in 41 (6.0%) vs 44 (6.3%) (OR, 0.95; 95% CI, 0.61-1.48; P = .82), respiratory failure in 38 (5.5%) vs 31 (4.4%) (OR, 1.27; 95% CI, 0.78-2.07; P = .34), and mortality within 30 days in 30 (4.4%) vs 20 (2.9%) (OR, 1.56; 95% CI, 0.88-2.77; P = .13). CONCLUSION Administration of 80% oxygen compared with 30% oxygen did not result in a difference in risk of surgical site infection after abdominal surgery. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00364741.

Increased Long-term Mortality After a High Perioperative Inspiratory Oxygen Fraction During Abdominal Surgery: Follow-up of a Randomized Clinical Trial

BACKGROUND:A high perioperative inspiratory oxygen fraction (80%) has been recommended to prevent postoperative wound infections. However, the most recent and one of the largest trials, the PROXI trial, found no reduction in surgical site infection, and 30-day mortality was higher in patients given 80% oxygen. In this follow-up study of the PROXI trial we assessed the association between long-term mortality and perioperative oxygen fraction in patients undergoing abdominal surgery. METHODS:From October 8, 2006, to October 6, 2008, 1386 patients underwent elective or emergency laparotomy and were randomized to receive either 80% or 30% oxygen during and for 2 hours after surgery. The follow-up date was February 24, 2010. Survival was analyzed using Kaplan-Meier statistics and the Cox proportional hazards model. RESULTS:Vital status was obtained in 1382 of 1386 patients after a median follow-up of 2.3 years (range 1.3 to 3.4 years). One hundred fifty-nine of 685 patients (23.2%) died in the 80% oxygen group compared to 128 of 701 patients (18.3%) assigned to 30% oxygen (HR, 1.30 [95% confidence interval, 1.03 to 1.64], P = 0.03). In patients undergoing cancer surgery, the HR was 1.45; 95% confidence interval, 1.10 to 1.90; P = 0.009; and after noncancer surgery, the HR was 1.06; 95% confidence interval, 0.69 to 1.65; P = 0.79. CONCLUSIONS:Administration of 80% oxygen in the perioperative period was associated with significantly increased long-term mortality and this appeared to be statistically significant in patients undergoing cancer surgery but not in noncancer patients.

Should Dosing of Rocuronium in Obese Patients Be Based on Ideal or Corrected Body Weight

BACKGROUND:Pharmacokinetic studies in obese patients suggest that dosing of rocuronium should be based on ideal body weight (IBW). This may, however, result in a prolonged onset time or compromised conditions for tracheal intubation. In this study, we compared onset time, conditions for tracheal intubation, and duration of action in obese patients when the intubation dose of rocuronium was based on three different weight corrections. METHODS:Fifty-one obese patients, with a median (range) body mass index of 44 (34–72) kg/m2, scheduled for laparoscopic gastric banding or gastric bypass under propofol-remifentanil anesthesia were randomized into three groups. The patients received rocuronium (0.6 mg/kg) based on IBW (IBW group, n = 17), IBW plus 20% of excess weight (corrected body weight [CBW]20% group, n = 17), or IBW plus 40% of excess weight (CBW40% group, n = 17). Propofol was administered as a bolus of 200 mg and an infusion at 5 mg · kg−1 · h−1 and remifentanil was administered at 1.0 &mgr;g · kg−1 · min−1, both according to CBW40%. Neuromuscular function was monitored with train-of-four nerve stimulation and acceleromyography. The primary end point was duration of action, defined as time to reappearance of the fourth twitch in train-of-four. RESULTS:The median (range) duration of action was 32 (18–49), 38 (25–66), and 42 (24–66) min in the IBW, CBW20%, and CBW40% groups, respectively (P = 0.001 for comparison of the IBW and CBW40% group). There were no significant differences in onset time (85 vs 84 vs 80 s) or in intubation conditions 90 s after administration of rocuronium. CONCLUSIONS:In obese patients undergoing gastric banding or gastric bypass, rocuronium dosed according to IBW provided a shorter duration of action without a significantly prolonged onset time or compromised conditions for tracheal intubation.

Perioperative Aspirin and Clonidine and Risk of Acute Kidney Injury A Randomized Clinical Trial

IMPORTANCE Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. OBJECTIVE To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. MAIN OUTCOMES AND MEASURES Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. RESULTS Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58). CONCLUSIONS AND RELEVANCE Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01082874.

Rational use of oxygen in medical disease and anesthesia.

PURPOSE OF REVIEW Supplemental oxygen is often administered during anesthesia and in critical illness to treat hypoxia, but high oxygen concentrations are also given for a number of other reasons such as prevention of surgical site infection (SSI). The decision to use supplemental oxygen is, however, controversial, because of large heterogeneity in the reported results and emerging reports of side-effects. The aim of this article is to review the recent findings regarding benefits and harms of oxygen therapy in anesthesia and acute medical conditions. RECENT FINDINGS Large randomized trials have not found significant reductions in SSI with 80% oxygen during and after abdominal surgery and cesarean section. There is no documented benefit of hyperbaric oxygen treatment for acute ischemic stroke, and there is emerging data to suggest increased mortality with normobaric supplemental oxygen for myocardial infarction without heart failure. Survival and neurologic outcome seem to be adversely affected by hyperoxia in patients with return of spontaneous circulation after cardiac arrest. SUMMARY The benefits of supplemental oxygen are not yet confirmed, and new findings suggest that potential side-effects should be considered if the inspired oxygen concentration is increased above what is needed to maintain normal arterial oxygen saturation.

Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial

BackgroundA high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (FiO2 = 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving FiO2 = 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery.Methods and designThe PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (FiO2 = 0.80) or 30% oxygen (FiO2 = 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power.DiscussionThis trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy.Trial registrationClinicalTrials.gov identifier: NCT00364741.

Inspiratory Oxygen Fraction and Postoperative Complications in Obese Patients A Subgroup Analysis of the PROXI Trial

Background:Obese patients are at a high risk of postoperative complication, including surgical site infection (SSI). Our aim was to evaluate the effect of a high inspiratory oxygen fraction (80%) on SSI and pulmonary complications in obese patients undergoing laparotomy. Methods:This study was a planned analysis of the obese patients (body mass index ≥ 30 kg/m2) recruited in the Danish multicenter, patient- and observer-blinded, PROXI Trial of 1,400 patients undergoing acute or elective laparotomy. Patients were randomized to receive either 80% or 30% oxygen during and for 2 h after surgery. The primary outcome was SSI within 14 days. Secondary outcomes were atelectasis, pneumonia, and respiratory failure. Results:Two hundred thirteen patients had a body mass index ≥ 30 kg/m2. The median (5–95% range) body mass index was 34 kg/m2 (30–44) and 33 kg/m2 (30–41) in patients allocated to the 80% and 30% oxygen group. SSI occurred in 32 of 102 (31%) versus 29 of 111 (26%) patients given 80% and 30% oxygen, respectively (odds ratio, 1.29; 95% CI, 0.71–2.34; P = 0.40). In addition, the incidence of pulmonary complications was not significantly different, with atelectasis occurring in 9% versus 6%, pneumonia in 6% versus 5%, and respiratory failure in 8% versus 5% in patients given 80% and 30% oxygen, respectively. Conclusion:Administration of 80% oxygen, compared with 30% oxygen, did not reduce the frequency of SSI in obese patients. Moreover, no significant association was found between oxygen fraction and the risk of pulmonary complications.

Risk of new or recurrent cancer after a high perioperative inspiratory oxygen fraction during abdominal surgery.

BACKGROUND Administration of supplemental oxygen in the perioperative period is controversial, as it may increase long-term mortality. Our aim was to assess the association between 80% oxygen and occurrence of subsequent cancer in patients undergoing abdominal surgery in a post hoc analysis of the PROXI trial. METHODS The 1386 patients in the PROXI trial underwent elective or emergency laparotomy between 2006 and 2008 with randomization to either 80% or 30% oxygen during and for 2 h after surgery. We retrieved follow-up status regarding vital status, new cancer diagnoses, and new histological cancer specimens. Data were analysed using the Cox proportional hazards model. RESULTS Follow-up was complete in 1377 patients (99%) after a median of 3.9 yr. The primary outcome of new cancer diagnosis or new malignant histological specimen occurred in 140 of 678 patients (21%) in the 80% oxygen group vs 150 of 699 patients (21%) assigned to 30% oxygen; hazards ratio 1.06 [95% confidence interval (CI) 0.84, 1.34], P=0.62. Cancer-free survival was significantly shorter in the 80% oxygen group; hazards ratio 1.19 (95% CI 1.01, 1.42), P=0.04, as was the time between surgery and new cancer, median 335 vs. 434 days in the 30% oxygen group. In patients with localized disease, non-significant differences in cancer and cancer-free survival were found with hazard ratios of 1.31 and 1.29, respectively. CONCLUSIONS Although new cancers occurred at similar rate, the cancer-free survival was significantly shorter in the 80% oxygen group, but this did not appear to explain the excess mortality in the 80% oxygen group. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov (NCT01723280).

Is it possible to predict hypotension during onset of spinal anesthesia in elderly patients

STUDY OBJECTIVE To evaluate the sensitivity and specificity of various predictors of hypotension during onset of spinal anesthesia in elderly patients. DESIGN Prospective study. SETTING 32 ASA physical status I, II, and III patients, aged >or=60 years, scheduled for elective lower limb surgery with spinal anesthesia. INTERVENTIONS Patients received spinal anesthesia with 10-17.5 mg of bupivacaine. No prophylactic ephedrine or fluid preloading was used. MEASUREMENTS A 5-minute baseline was recorded and during onset of spinal anesthesia, hemodynamic changes were measured every 10 seconds from the radial artery pressure curve. Data collection ended when patients were ready for surgery, or if ephedrine was given to increase mean arterial pressure. MAIN RESULTS 21 patients had hypotension. Baseline blood pressure variability low-frequency band power (BPV LF) >8 mmHg(2) and near-infrared spectroscopy (NIRS) reduction >or=5% had high sensitivity (0.73 and 0.90, respectively) and specificity (0.78 and 0.64, respectively), and were significantly associated with the development of hypotension. CONCLUSIONS Only NIRS and BPV LF could significantly predict hypotension among the elderly.

Clinical relevance of surgical site infection as defined by the criteria of the Centers for Disease Control and Prevention.

Surgical site infection (SSI) is a common complication after abdominal surgery and the Centers for Disease Control and Prevention (CDC) criteria are commonly used for diagnosis and surveillance. The aim of this study was to evaluate whether SSI diagnosed according to CDC is clinically relevant (CRSSI) and whether there is agreement between evaluations according to the CDC criteria, the ASEPSIS score (Additional treatment, presence of Serous discharge, Erythema, Purulent exudate, Separation of the deep tissues, Isolation of bacteria and duration of Stay) and CRSSI. We included 54 patients diagnosed with SSI and a matched control group (N=46) without SSI according to the CDC criteria after laparotomy. Two blinded experienced surgeons evaluated the hospital records and determined whether patients had CRSSI, based on the following criteria: antibiotic treatment, surgical intervention, prolonged hospital stay or referral to an intensive care unit for SSI. The rate of CRSSI was 38 of 54 (70%) in patients with CDC-diagnosed SSI and none in patients without a CDC-diagnosed SSI. Sixty-one percent of the CDC-diagnosed SSIs were superficial, of which 48% were considered clinically relevant. There was substantial agreement between the CDC criteria and CRSSI [kappa=0.69; 95% confidence interval (CI): 0.55-0.83] and fair agreement between the ASEPSIS score and the CDC criteria (kappa=0.23; 95% CI: 0-0.49) and between the ASEPSIS score and CRSSI (kappa=0.39; 95% CI: 0.17-0.61). The CDC criteria represent a suitable standard definition for monitoring and identifying SSI, even if some cases of less clinically significant superficial SSI are included.