Dexamethasone and Surgical-Site Infection Corcoran, Tomás B; Myles, Paul S; Forbes, Andrew B ...
New England journal of medicine/The New England journal of medicine,
05/2021, Letnik:
384, Številka:
18
Journal Article
Recenzirano
Odprti dostop
In this trial involving patients undergoing noncardiac surgery, dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after surgery, ...including in patients with diabetes mellitus.
Patients undergoing major abdominal surgery received restrictive or liberal intravenous fluids during surgery and up to 24 hours thereafter. The restrictive regimen did not improve disability-free ...survival and resulted in increased acute kidney injury.
BACKGROUND:Glucocorticoids are increasingly used perioperatively, principally to prevent nausea and vomiting. Safety concerns focus on the potential for hyperglycemia and increased infection. The ...authors hypothesized that glucocorticoids predispose to such adverse outcomes in a dose-dependent fashion after elective noncardiac surgery.
METHODS:The authors conducted a systematic literature search of the major medical databases from their inception to April 2016. Randomized glucocorticoid trials in adults specifically reporting on a safety outcome were included and meta-analyzed with Peto odds ratio method or the quality effects model. Subanalyses were performed according to a dexamethasone dose equivalent of low (less than 8 mg), medium (8 to 16 mg), and high (more than 16 mg). The primary endpoints of any wound infection and peak perioperative glucose concentrations were subject to meta-regression.
RESULTS:Fifty-six trials from 18 countries were identified, predominantly assessing dexamethasone. Glucocorticoids did not impact on any wound infection (odds ratio, 0.8; 95% CI, 0.6 to 1.2) but did result in a clinically unimportant increase in peak perioperative glucose concentration (weighted mean difference, 20.0 mg/dl; CI, 11.4 to 28.6; P < 0.001 or 1.1 mM; CI, 0.6 to 1.6). Glucocorticoids reduced peak postoperative C-reactive protein concentrations (weighted mean difference, −22.1 mg/l; CI, −31.7 to −12.5; P < 0.001), but other adverse outcomes and length of stay were unchanged. No dose–effect relationships were apparent.
CONCLUSIONS:The evidence at present does not highlight any safety concerns with respect to the use of perioperative glucocorticoids and subsequent infection, hyperglycemia, or other adverse outcomes. Nevertheless, collated trials lacked sufficient surveillance and power to detect clinically important differences in complications such as wound infection.
Dexamethasone is commonly administered intraoperatively to prevent postoperative nausea and vomiting and is believed to have analgesic properties. It is unknown whether it has an impact on chronic ...wound pain.
In this prespecified embedded superiority substudy of the randomised PADDI trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and were followed up for 6 months postoperatively. The primary outcome was the incidence of pain in the surgical wound at 6 months. Secondary outcomes included acute postoperative pain and correlates of chronic postsurgical pain.
We included 8478 participants in the modified intention-to-treat population (4258 in the dexamethasone group and 4220 in the matched placebo group). The primary outcome occurred in 491 subjects (11.5%) in the dexamethasone arm and 404 (9.6%) subjects in the placebo arm (relative risk 1.2, 95% confidence interval 1.06–1.41, P=0.003). Maximum pain scores at rest and on movement in the first 3 postoperative days were lower in the dexamethasone group compared with the control group {median 5 (inter-quartile range IQR 3.0–8.0) vs 6 (IQR 3.0–8.0) and median 7 (IQR 5.0–9.0) vs 8 (IQR 6.0–9.0), P<0.001 for both}. Severity of postoperative pain was not predictive of chronic postsurgical pain. The severity of chronic postsurgical pain and the frequency of neuropathic features did not differ between treatment groups.
Administration of dexamethasone 8 mg i.v. was associated with an increase in the risk of pain in the surgical wound 6 months after surgery.
ACTRN12614001226695.
Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has ...on this experience.
In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately.
A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk RR=0.79; 95% confidence interval CI, 0.56–1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37–0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20–202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery.
Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents.
ACTRN12614001226695.
Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown.
This retrospective cohort study analysed prospective data obtained ...from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery.
A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval CI, 76.7–80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio RR=1.51; 95% CI, 1.10–2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87–119) vs 114 (95% CI, 99–128; P<0.001), and 130 (95% CI, 112–140) vs 139 (95% CI, 121–144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55–42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65–4.23; P<0.001); and longer median (inter-quartile range IQR) hospital stays, 6.6 (4.4–12.4) vs 3.7 (2.5–6.5) days (P<0.001).
Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated.
NCT04978285 (ClinicalTrials.gov).
Dexamethasone has been shown to reduce acute pain after surgery, but there is uncertainty as to its effects on chronic postsurgical pain (CPSP). We hypothesised that in patients undergoing major ...noncardiac surgery, a single intraoperative dose of dexamethasone increases the incidence of CPSP.
We devised a propensity score-matched analysis of the ENIGMA-II trial CPSP dataset, aiming to compare the incidence of CPSP in patients who had received dexamethasone or not 12 months after major noncardiac surgery. The primary outcome was the incidence of CPSP. We used propensity score matching and inverse probability weighting to balance baseline variables to estimate the average marginal effect of dexamethasone on patient outcomes, accounting for confounding to estimate the average treatment effect on those treated with dexamethasone.
We analysed 2999 patients, of whom 116 of 973 (11.9%) receiving dexamethasone reported CPSP, and 380 of 2026 (18.8%) not receiving dexamethasone reported CPSP, unadjusted odds ratio 0.76 (95% confidence interval 0.78–1.00), P=0.052. After propensity score matching, CPSP occurred in 116 of 973 patients (12.2%) receiving dexamethasone and 380 of 2026 patients (13.8%) not receiving dexamethasone, adjusted risk ratio 0.88 (95% confidence interval 0.61–1.27), P=0.493. There was no difference between groups in quality of life or pain interference with daily activities, but ‘least pain’ (P=0.033) and ‘pain right now’ (P=0.034) were higher in the dexamethasone group.
Dexamethasone does not increase the risk of chronic postsurgical pain after major noncardiac surgery.
Open Science Framework Registration DOI https://doi.org/10.17605/OSF.IO/ZDVB5.
BACKGROUNDThe hyperglycaemic effect of dexamethasone in diabetic and nondiabetic patients in the peri-operative period is unknown.
OBJECTIVETo assess the effect of a single dose of intra-operative ...dexamethasone on peri-operative blood glucose.
DESIGNMulticentre, stratified, randomised trial.
SETTINGUniversity hospitals in Australia and Hong Kong.
PATIENTSA total of 302 adults scheduled for elective, noncardiac and nonobstetric surgical procedures under general anaesthesia, stratified by diabetes mellitus status, were randomised to receive placebo, 4 or 8 mg dexamethasone administered intravenously after induction of anaesthesia.
MAIN OUTCOME MEASURESMaximum blood glucose within 24 h of surgery, and the interaction between glycated haemoglobin (HbA1c) and dexamethasone were the primary and secondary outcomes.
RESULTSThe median IQR baseline blood glucose in the nondiabetes stratum in the placebo (n=81), 4 mg (n=81) and 8 mg dexamethasone (n=77) trial arms were respectively 5.3 4.6 to 5.8, 5.0 4.7 to 5.4 and 5.0 4.2 to 5.9 mmol l. In the diabetes stratum these values were 6.6 6.0 to 8.3; (n=22), 6.1 5.5 to 10.4; (n=22) and 6.7 5.6 to 8.3; (n=19) mmol l. The median IQR maximum peri-operative blood glucose values in the nondiabetes stratum were 6.0 5.3 to 6.8, 6.3 5.5 to 7.3 and 6.3 5.8 to 7.4 mmol l in the control, dexamethasone 4 mg and dexamethasone 8 mg arms, respectively. In the diabetes stratum these values were 10.3 8.1 to 12.4, 12.6 10.3 to 18.3 and 13.6 11.2 to 0.1 mmol l. There was a significant interaction between pre-operative HbA1c value and 8 mg dexamethasoneevery 1% increment in HbA1c produced a 4.0 mmol l elevation in maximal peri-operative glucose concentration.
CONCLUSIONDexamethasone four or 8 mg did not induce greater hyperglycaemia compared with placebo for nondiabetic and well controlled diabetic patients. Maximal peri-operative blood glucose concentrations in patients with diabetes were related to baseline HbA1c values in a concentration-dependent fashion after 8 mg of dexamethasone.
TRIAL REGISTRATIONAustralia and New Zealand Clinical Trials Registry (ACTRN12614001145695)URLhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367272.
The level of inspired oxygen during surgery may modify free radical release, and reperfusion injury. This controlled trial examined the effect of inspired oxygen on F
2
-isoprostanes (F
2
-IsoPs), ...isofurans (IsoFs), and specialized mediators of inflammation resolution (SPM) during knee replacement surgery. Patients received either 30% O
2
(control n = 21), 50% O
2
(n = 20), or 80% O
2
(n = 19) O
2
, in a parallel design. Hemoglobin (Hb) was measured throughout the surgery and F
2
-IsoPs, IsoFs and SPM were analyzed by mass spectrometry. The effect of O
2
on F
2
-IsoPs and IsoFs was examined during tourniquet inflation and after tourniquet release. SPM were measured at baseline and the end of surgery. There was a significant interaction between O
2
and Hb concentrations with plasma IsoFs during tourniquet inflation. An increase in plasma IsoFs over time was attenuated in the 80% O
2
group (p=.012) compared with the 30% O
2
group after adjusting for Hb concentration. After tourniquet release, plasma F
2
-IsoPs were significantly lower in the 50% and 80% O
2
groups (p=.009 and p=.001, respectively) compared with the 30% O
2
group after adjustment for Hb concentration. The SPM RvD2 and RvE2 were increased with 50% and 80% O
2
(RvD2, p=.014 and p=.002, respectively; RvE2, p=.032 with 50% O
2
) compared with the 30% O
2
group, in analyses that corrected for Hb concentration. We have shown for the first time that higher O
2
levels may be beneficial in reducing oxidative stress and increasing resolution of inflammation during surgery that involves reperfusion after application of a tourniquet.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We compared baseline characteristics and outcomes and evaluated the subgroup effects of randomised interventions by sex in males and females in large international perioperative trials.
Nine ...randomised trials and two cohort studies recruiting adult patients, conducted between 1995 and 2020, were included. Baseline characteristics and outcomes common to six or more studies were evaluated. Regression models included terms for sex, study, and an interaction between the two. Comparing outcomes without adjustment for baseline characteristics represents the ‘total effect’ of sex on the outcome.
Of 54 626 participants, 58% were male and 42% were female. Females were less likely to have ASA physical status ≥3 (56% vs 64%), to smoke (15% vs 23%), have coronary artery disease (21% vs 32%), or undergo vascular surgery (10% vs 23%). The pooled incidence of death was 1.6% in females and 1.8% in males (risk ratio RR 0.92; 95% confidence interval CI: 0.81–1.05; P=0.20), of myocardial infarction was 4.2% vs 4.5% (RR 0.92; 95% CI: 0.81–1.03; P=0.10), of stroke was 0.5% vs 0.6% (RR 1.03; 95% CI: 0.79–1.35; P=0.81), and of surgical site infection was 8.6% vs 8.3% (RR 1.03; 95% CI: 0.79–1.35; P=0.70). Treatment effects of three interventions demonstrated statistically significant effect modification by sex.
Females were in the minority in all included studies. They were healthier than males, but outcomes were comparable. Further research is needed to understand the reasons for this discrepancy.
International Registry of Meta-Research (UID: IRMR_000011; 5 January 2021).
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