BACKGROUND: A number of perioperative risk factors may suppress the immune system and contribute to the development of post-operative complications. The association between surgical site infection (SSI) and other wound-related complications resulting from immunosuppression through either perioperative administration of dexamethasone, pre-operative smoking or alcohol abuse is, however, uncertain.
METHODS: This study was a post hoc analysis of data from the PROXI randomized trial in 1386 patients who underwent emergency or elective laparotomy. We assessed the associations of use of dexamethasone, smoking status and alcohol abuse with the primary outcome, being a composite of SSI, anastomotic leak, wound dehiscence, burst abdomen and 30-day mortality.
RESULTS: The primary outcome occurred in 21% of patients receiving dexamethasone versus 28% of patients not receiving dexamethasone, and this was not statistically significant when adjusting for stratification variables originally used in the PROXI trial [OR 0.90, 95% CI (0.65-1.24)]. In smokers, the primary outcome occurred in 32%, compared with 23% of non-smokers (P = 0.0001). Smokers also had a higher frequency of SSI (25% vs 17%, P < 0.0001) and burst abdomen (3.8% vs 2.4%, P = 0.04). In alcohol abusers, the primary outcome occurred in 48%, compared with 25% in patients who did not abuse alcohol (P = 0.0006). Burst abdomen occurred more commonly in alcohol abusers (15% vs 2.3%, P < 0.0001).
CONCLUSION: Perioperative administration of dexamethasone was not significantly associated with SSI or other wound-related complications. Conversely, smoking and alcohol abuse were both significant predictors of the primary outcome consisting of wound-related complications and mortality.
BACKGROUND: Dexamethasone is widely used for postoperative nausea and vomiting (PONV) prophylaxis. However, there are limited data on the risk of wound complications associated with single-dose dexamethasone use for this purpose. We performed this retrospective study to determine whether intraoperative dexamethasone for PONV prevention increases the risk or severity of postoperative wound complications.
METHODS: Women who underwent laparotomy for endometrial cancer between 2002 and 2007 were identified from a tumor registry. Perioperative records were reviewed to determine dexamethasone administration. Medical records were reviewed to identify wound complications including cellulitis, superficial surgical site infection, wound separation, and fascial dehiscence. Wound care needs and time to complete wound healing were compared based on dexamethasone exposure. The rate of wound complications was also compared based on dexamethasone dose. Baseline characteristics and perioperative details were evaluated for independent associations with wound complications. Logistic regression analyses were performed to predict the occurrence of wound complications.
RESULTS: Four hundred thirty-one patients met inclusion criteria; 192 (44.6%) received dexamethasone (4-12 mg) and 31.1% developed a wound complication. In unadjusted analysis, there was no difference in the risk of developing a wound complication based on dexamethasone exposure; 53 of 192 patients (27.6%) who received dexamethasone developed a wound complication, compared with 81 of 239 (33.9%) who did not receive dexamethasone: odds ratio (OR) (95% confidence interval [CI]) = 0.74 (0.49, 1.13), P = 0.16. There was no difference in the distribution of wound complication types based on receipt of dexamethasone (P = 0.71), or in the incidence of wound complications based on the dose of dexamethasone (P = 0.48). Of patients who developed a wound complication, there was no difference in the need for IV antibiotics, vacuum-assisted wound closure, or in the rate of fascial dehiscence based on dexamethasone exposure. The time to complete wound healing was not different between the 2 cohorts (P = 0.48). In univariate analysis, higher body mass index (BMI), higher estimated blood loss, smoking, and longer duration of surgery were predictors of wound complications. Smoking (OR [95% CI]: 2.0 [1.3, 3.2], P = 0.003) and BMI (OR [95% CI]: 1.2 [1.1, 1.3], P = 0.0003) were the only significant predictors of wound complications in the multivariate model, whereas dexamethasone remained a nonsignificant predictor (OR [95% CI]: 0.7 [0.5, 1.1], P = 0.12).
CONCLUSION: Intraoperative dexamethasone for PONV prophylaxis does not seem to increase the rate or severity of postoperative wound complications in women undergoing laparotomy for endometrial cancer. BMI and smoking were significant predictors of wound complications in this patient population.
<b>CONTEXT: </b>Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking.<b>OBJECTIVE: </b>To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery.<b>Design, Setting, and Participants: </b>A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011.<b>Intervention: </b>Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255).<b>MAIN OUTCOME MEASURES: </b>A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization.<b>RESULTS: </b>Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels.<b>CONCLUSION: </b>In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo.<b>Trial Registration: </b>clinicaltrials.gov Identifier: NCT00293592.
OBJECTIVES: To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection.
DESIGN: Cohort study based on data from a prospective clinical database and electronically registered medical records.
SETTING: Six major colorectal centres in eastern Denmark.
PARTICIPANTS: 2766 patients (1441 (52%) men) undergoing elective operation for colorectal cancer with colonic or rectal resection and primary anastomosis between 1 January 2006 and 31 December 2009. Median age was 70 years (interquartile range 62-77).
INTERVENTION: Postoperative use of NSAID (defined as at least two days of NSAID treatment in the first seven days after surgery).
MAIN OUTCOME MEASURES: Frequency of clinical anastomotic leakage verified at reoperation; mortality at 30 days.
RESULTS: Of 2756 patients with available data and included in the final analysis, 1871 (68%) did not receive postoperative NSAID treatment (controls) and 885 (32%) did. In the NSAID group, 655 (74%) patients received ibuprofen and 226 (26%) received diclofenac. Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment, compared with controls (12.8% and 8.2% v 5.1%; P<0.001). After unadjusted analyses and when compared with controls, more patients had anastomotic leakage after treatment with diclofenac (7.8% (95% confidence interval 3.9% to 12.8%)) and ibuprofen (3.2% (1.0% to 5.7%)). But after multivariate logistic regression analysis, only diclofenac treatment was a risk factor for leakage (odds ratio 7.2 (95% confidence interval 3.8 to 13.4), P<0.001; ibuprofen 1.5 (0.8 to 2.9), P=0.18). Other risk factors for anastomotic leakage were male sex, rectal (v colonic) anastomosis, and blood transfusion. 30 day mortality was comparable in the three groups (diclofenac 1.8% v ibuprofen 4.1% v controls 3.2%; P=0.20).
CONCLUSIONS: Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery. Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis. Large scale, randomised controlled trials are urgently needed.
BACKGROUND: With the implementation of multimodal analgesia regimens in fast-track surgery programmes, non-steroidal anti-inflammatory drugs (NSAIDs) are being prescribed routinely. However, doubts have been raised concerning the safety of NSAIDs in terms of anastomotic healing.
METHODS: Data on patients who had undergone primary colorectal anastomosis at two teaching hospitals between January 2008 and December 2010 were analysed retrospectively. Exact use of NSAIDs was recorded. Rates of anastomotic leakage were compared between groups and corrected for known risk factors in both univariable and multivariable analyses.
RESULTS: A total of 795 patients were divided into four groups according to NSAID use: no NSAIDs (471 patients), use of non-selective NSAIDs (201), use of selective cyclo-oxygenase (COX) 2 inhibitors (79), and use of both selective and non-selective NSAIDs (44). The overall leak rate was 9.9 per cent (10.0 per cent for right colonic, 8.7 per cent for left colonic and 12.4 per cent for rectal anastomoses). Known risk factors such as smoking and use of steroids were not significantly associated with anastomotic leakage. Stapled anastomosis was identified as an independent predictor of leakage in multivariable analysis (odds ratio (OR) 2.22, 95 per cent confidence interval 1.30 to 3.80; P = 0.003). Patients on NSAIDs had higher anastomotic leakage rates than those not on NSAIDs (13.2 versus 7.6 per cent; OR 1.84, 1.13 to 2.98; P = 0.010). This effect was mainly due to non-selective NSAIDs (14.5 per cent; OR 2.13, 1.24 to 3.65; P = 0.006), not selective COX-2 inhibitors (9 per cent; OR 1.16, 0.49 to 2.75; P = 0.741). The overall mortality rate was 4.2 per cent, with no significant difference between groups (P = 0.438).
CONCLUSION: Non-selective NSAIDs may be associated with anastomotic leakage.
OBJECTIVES: To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain.
METHODS: A randomised, double-blind, four-arm, parallel-group, active controlled trial investigating short-term (day 10) and long-term (week 13) benefits and side-effects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fixed-dose combination tablet (ibuprofen 200 mg/paracetamol 500 mg); two fixed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg).
RESULTS: There were 892 participants (mean age 60.6, range 40-84 years); 63% had radiographic knee osteoarthritis and 85% fulfilled American College of Rheumatology criteria for osteoarthritis. At day 10, two combination tablets were superior to paracetamol (p<0.01) for pain relief (determined by mean change from baseline in WOMAC pain; n=786). At 13 weeks, significantly more participants taking one or two combination tablets rated their treatment as excellent/good compared with paracetamol (p=0.015, p=0.0002, respectively; n=615). The frequency of adverse events was comparable between groups. However, by 13 weeks, decreases in haemoglobin (≥1 g/dl) were observed in some participants in all groups. Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy (p<0.001; paracetamol, 20.3%; ibuprofen, 19.6%; one or two combination tablets, 24.1%, 38.4%, respectively).
CONCLUSIONS: Ibuprofen/paracetamol combination analgesia, at non-prescription doses, confers modest short-term benefits for knee pain/osteoarthritis. However, in this population, paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day, and the combination of the two appears to be additive. Study no ISRCTN77199439.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are widely used analgesics in the prescription and non-prescription settings. Although both classes of drug are generally well tolerated, they can lead to well-characterized adverse effects. Both drugs are widely co-prescribed and it is of interest to understand better safety outcomes when the two drugs are taken concomitantly. WHAT THIS STUDY ADDS?: Relative rates and hazard ratio patterns of safety outcomes were broadly similar for patients prescribed ibuprofen alone, paracetamol alone and concomitant ibuprofen and paracetamol. The risks of the various safety outcomes examined do not appear to be modified by concomitant use of ibuprofen and paracetamol compared with paracetamol or ibuprofen alone.
AIMS: To evaluate and compare the risk of specific safety outcomes in patients prescribed ibuprofen and paracetamol concomitantly with those in patients prescribed ibuprofen or paracetamol alone. The outcomes were evaluated according to dose, duration and exposure.
METHODS: The study used a retrospective longitudinal cohort design with data from the UK General Practice Research Database (GPRD). The study population included patients aged 18 years or over who were prescribed ibuprofen alone, paracetamol alone or concomitant ibuprofen and paracetamol (tablets or capsules only). The safety outcomes evaluated were upper gastrointestinal events, myocardial infarction, stroke, renal failure (excluding chronic), congestive heart failure, intentional or accidental overdose, suicidal behaviour and mortality. Time-dependent Cox regression was used to estimate relative rates for the safety outcomes, by treatment group. A further analysis evaluated whether the hazard rates (i.e. absolute risks) varied over time with changes in drug exposure.
RESULTS: The study population included 1.2 million patients. There was considerable heterogeneity in both patient and exposure characteristics. When comparing with past users, for most safety outcomes, current users of concomitant paracetamol and ibuprofen had relative rates between those for current users of ibuprofen alone and paracetamol alone. The hazard rates were generally proportional over time, from current to past exposure, following a prescription for concomitant paracetamol and ibuprofen compared with ibuprofen alone or paracetamol alone.
CONCLUSIONS: The known risk of the safety outcomes examined does not appear to be modified by concomitant use of ibuprofen and paracetamol compared with paracetamol or ibuprofen alone.
BACKGROUND: Anastomotic leakage occurs after 3-6 per cent of colonic resections. The influence of analgesic agents is largely unknown. This study determined the rate of anastomotic leakage in a series of patients who had colonic surgery over a 9-year period with or without use of a cyclo-oxygenase inhibitor for postoperative analgesia.
METHODS: Patients with anastomotic leakage following a standard fast-track procotol between April 1997 and May 2006 were identified from a prospective, consecutive database. During this period there were two changes in perioperative management: cessation of preoperative oral bowel preparation in August 2002 and the use of celecoxib for postoperative analgesia between May 2003 and November 2004. Rates of anastomotic leakage during the various periods were determined and compared.
RESULTS: Some 28 (5.6 per cent) of 502 patients had an anastomotic leak. The incidence of leakage increased significantly during the period of celecoxib use (15.1 per cent), versus 3.3 and 1.5 per cent respectively before and after celecoxib use (P < 0.001). Leakage rates were similar with or without oral bowel preparation (3.5 versus 1.7 per cent respectively; P = 0.346) when celecoxib was not used.
CONCLUSION: A detrimental effect of celecoxib on anastomotic healing is suggested, and requires further evaluation.
A number of perioperative risk factors may suppress the immune system and contribute to the development of post-operative complications. The association between surgical site infection (SSI) and other wound-related complications resulting from immunosuppression through either perioperative administration of dexamethasone, pre-operative smoking or alcohol abuse is, however, uncertain.
METHODS:
This study was a post hoc analysis of data from the PROXI randomized trial in 1386 patients who underwent emergency or elective laparotomy. We assessed the associations of use of dexamethasone, smoking status and alcohol abuse with the primary outcome, being a composite of SSI, anastomotic leak, wound dehiscence, burst abdomen and 30-day mortality.
RESULTS:
The primary outcome occurred in 21% of patients receiving dexamethasone versus 28% of patients not receiving dexamethasone, and this was not statistically significant when adjusting for stratification variables originally used in the PROXI trial [OR 0.90, 95% CI (0.65-1.24)]. In smokers, the primary outcome occurred in 32%, compared with 23% of non-smokers (P = 0.0001). Smokers also had a higher frequency of SSI (25% vs 17%, P < 0.0001) and burst abdomen (3.8% vs 2.4%, P = 0.04). In alcohol abusers, the primary outcome occurred in 48%, compared with 25% in patients who did not abuse alcohol (P = 0.0006). Burst abdomen occurred more commonly in alcohol abusers (15% vs 2.3%, P < 0.0001).
CONCLUSION:
Perioperative administration of dexamethasone was not significantly associated with SSI or other wound-related complications. Conversely, smoking and alcohol abuse were both significant predictors of the primary outcome consisting of wound-related complications and mortality.
