Pernille L. Petersen

Effect of perioperative β blockade in patients with diabetes undergoing major non-cardiac surgery: randomised placebo controlled, blinded multicentre trial

Abstract Objectives To evaluate the long term effects of perioperative β blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University anaesthesia and surgical centres and one coordinating centre. Participants 921 patients aged > 39 scheduled for major non-cardiac surgery. Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. Main outcome measures The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity. Results Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% (− 0.8% to 5.6%). Conclusions Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment. Trial registration Current Controlled Trials ISRCTN58485613 [controlled-trials.com.

Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial.

Objective:For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival. Design:Randomized controlled open-label trial. Setting:Nine multidisciplinary intensive care units across Denmark. Patients:A total of 1,200 critically ill patients were included after meeting the following eligibility requirements: expected intensive care unit stay of ≥24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive). Interventions:Patients were randomized either to the “standard-of-care-only arm,” receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the “procalcitonin arm,” in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements. Measurements and Main Results:The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval [CI] −4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0–6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m2 was 1.21 (95% CI, 1.15–1.27). Conclusions:Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.

The transversus abdominis plane block: a valuable option for postoperative analgesia? A topical review

The transversus abdominis plane (TAP) block is a newly described peripheral block involving the nerves of the anterior abdominal wall. The block has been developed for post‐operative pain control after gynaecologic and abdominal surgery. The initial technique described the lumbar triangle of Petit as the landmark used to access the TAP in order to facilitate the deposition of local anaesthetic solution in the neurovascular plane. Other techniques include ultrasound‐guided access to the neurovascular plane via the mid‐axillary line between the iliac crest and the costal margin, and a subcostal access termed the ‘oblique subcostal’ access. A systematic search of the literature identified a total of seven randomized clinical trials investigating the effect of TAP block on post‐operative pain, including a total of 364 patients, of whom 180 received TAP blockade. The surgical procedures included large bowel resection with a midline abdominal incision, caesarean delivery via the Pfannenstiel incision, abdominal hysterectomy via a transverse lower abdominal wall incision, open appendectomy and laparoscopic cholecystectomy. Overall, the results are encouraging and most studies have demonstrated clinically significant reductions of post‐operative opioid requirements and pain, as well as some effects on opioid‐related side effects (sedation and post‐operative nausea and vomiting). Further studies are warranted to support the findings of the primary published trials and to establish general recommendations for the use of a TAP block.

The Beneficial Effect of Transversus Abdominis Plane Block After Laparoscopic Cholecystectomy in Day-Case Surgery: A Randomized Clinical Trial

BACKGROUND: Laparoscopic cholecystectomy is associated with postoperative pain of moderate intensity in the early postoperative period. Recent randomized trials have demonstrated the efficacy of transversus abdominis plane (TAP) block in providing postoperative analgesia after abdominal surgery. We hypothesized that a TAP block may reduce pain while coughing and at rest for the first 24 postoperative hours, opioid consumption, and opioid side effects in patients undergoing laparoscopic cholecystectomy in day-case surgery. METHODS: In this randomized, double-blind study, 80 patients undergoing laparoscopic cholecystectomy in our day-case surgery unit were allocated to receive either bilateral ultrasound-guided posterior TAP blocks (20 mL 0.5% ropivacaine) or placebo blocks. Postoperative pain treatment consisted of oral acetaminophen 1000 mg × 4, oral ibuprofen 400 mg × 3, IV morphine (0–2 hours postoperatively), and oral ketobemidone (2–24 hours postoperatively). The primary outcome was postoperative pain scores while coughing calculated as area under the curve for the first 24 postoperative hours (AUC/24 h). Secondary outcomes were pain scores at rest (AUC/24 h), opioid consumption, and side effects. Patients were assessed 0, 2, 4, 6, 8, and 24 hours postoperatively. Group-wise comparisons of visual analog scale (VAS) pain (AUC/24 h) were performed with the 2-sample t test. Morphine and ketobemidone consumption were compared with the Mann-Whitney test for unpaired data. Categorical data were analyzed using the &khgr;2 test. RESULTS: The primary outcome variable, VAS pain scores while coughing (AUC/24 h), was significantly reduced in the TAP versus the placebo group (P = 0.04); group TAP: 26 mm (SD 13) (weighted average level) versus group placebo: 34 (18) (95% confidence interval): 0.5–15 mm). VAS pain scores at rest (AUC/24 h) showed no significant difference between groups. Median morphine consumption (0–2 hours postoperatively) was 7.5 mg (interquartile range: 5–10 mg) in the placebo group compared with 5 mg (interquartile range: 0–5 mg) in the TAP group (P < 0.001). The odds ratio of a random patient in group TAP having less morphine consumption than a random patient in group placebo was P (group TAP < group placebo) = 0.26 (confidence interval: 0.15, 0.37) where 0.5 represents no difference between groups. There were no between-group differences in total ketobemidone consumption, levels of nausea and sedation, number of patients vomiting, or consumption of ondansetron. CONCLUSIONS: TAP block after laparoscopic cholecystectomy may have some beneficial effect in reducing pain while coughing and on opioid requirements, but this effect is probably rather small.

The effect of transversus abdominis plane block or local anaesthetic infiltration in inguinal hernia repair: a randomised clinical trial.

CONTEXT The analgesic effect of transversus abdominis plane (TAP) block after inguinal hernia repair is unclear. OBJECTIVE The aim of this randomised and double-blind study was to evaluate the analgesic effect of a TAP block in patients scheduled for primary inguinal hernia repair. The TAP block was evaluated versus placebo and versus an active comparator (ilioinguinal block and wound infiltration). DESIGN Randomised controlled trial. SETTING Single centre trial. Study period from June 2010 to November 2011. PATIENTS Adults (18 to 75 years) with American Society of Anesthesiologists’ status 1–3 scheduled for primary inguinal hernia repair as day case surgery were included in the study. INTERVENTIONS Ninety patients were allocated to one of three groups: group TAP, group infiltration (ilioinguinal nerve block and wound infiltration) and group placebo. MAIN OUTCOME MEASURES The primary outcome measure was pain scores while coughing between group TAP and group placebo calculated as area under the curve for the first 24 h (AUC24 h). Secondary outcomes were pain scores while coughing and at rest, opioid consumption and side effects in groups TAP, infiltration and placebo. RESULTS Visual analogue pain scores while coughing and at rest demonstrated no difference between groups. Pain scores in groups infiltration, TAP and placebo were 19 versus 22 versus 15 mm at rest (P = 1.00) and 37 versus 41 versus 37 mm while coughing (P = 1.00). Pain scores at 6 h (AUC6 h) were significantly lower in group infiltration than in group TAP (10 versus 25 mm at rest, P < 0.001; 17 versus 40 mm while coughing, P < 0.001), and than in group placebo (10 versus 20 mm at rest, P = 0.003; 17 versus 38 mm while coughing, P < 0.001). Median morphine consumption was lower in group infiltration than in group placebo (0 versus 5 mg, P < 0.003). No differences among groups were demonstrated for ketobemidone consumption or side effects. CONCLUSION Ultrasound-guided TAP block did not reduce postoperative pain after inguinal hernia repair. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01052285. EudraCT number 2010–018403-29.

Gabapentin for post-operative pain management – a systematic review with meta-analyses and trial sequential analyses

Perioperative pain treatment often consist of combinations of non‐opioid and opioid analgesics, ‘multimodal analgesia’, in which gabapentin is currently used. The aim was to document beneficial and harmful effects of perioperative gabapentin treatment.

Bilateral transversus abdominis plane (TAP) block with 24 hours ropivacaine infusion via TAP catheters: A randomized trial in healthy volunteers

BackgroundThe analgesic effect of a TAP block has been investigated in various surgical settings. There are however limited information about block level and block duration. Furthermore, there is a lack of information about continuous TAP block after ultrasound-guided posterior TAP blocks.The aim of this double-blind randomized study was therefore to investigate the effect of an ultrasound-guided posterior TAP block with 24 hours local anesthetic infusion via a TAP catheter.MethodsIn this randomized study 8 male volunteers received a bilateral TAP block (20 mLs 0.5% ropivacaine) and were allocated to receive active infusion (ropivacaine 0.2% 5 mL/hr) via a TAP catheter on one side and placebo infusion on the other side. Primary outcome: Dermatomal sensory block involvement after 24 hours evaluated with pinprick. Secondary outcomes: Sensory block involvement evaluated with cold test and heat-pain detection thresholds (HPDT) on the abdominal wall. Assessment points: 15 min before block performance and 1, 4, 8, 12 and 24 hours after block performance.ResultsThe TAP block primarily involved sensory changes in the Th10 to Th12 dermatomes. On the placebo side there was a decrease in extension beginning at 4–8 hours after block performance and with no detectable effect beyond 12 hours. Median number of dermatomes anesthetized (pinprick) at 24 hours after block performance was 1.5 (0–3) on the active side compared with 0 (0–0) on the placebo side (P = 0.039).There were no statistical significant between-side differences in HPDT measurements at 24 hours after block performance.ConclusionsThe spread of sensory block following ultrasound-guided posterior TAP block is partly maintained by a continuous 24 hour ropivacaine infusion through a TAP catheter.Trial registrationThe study was registered at NCT01577940

Transversus abdominis plane (TAP) block after robot‐assisted laparoscopic hysterectomy: a randomised clinical trial

Transversus abdominis plane (TAP) block is widely used as a part of pain management after various abdominal surgeries. We evaluated the effect of TAP block as an add‐on to the routine analgesic regimen in patients undergoing robot‐assisted laparoscopic hysterectomy.

Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta-analyses and trial sequential analyses

Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Petos odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.

Transversus abdominis plane block after laparoscopic colonic resection in cancer patients: A randomised clinical trial.

BACKGROUNDA key point in pathways for optimal rehabilitation and enhanced recovery is an effective postoperative multimodal pain treatment regimen. OBJECTIVETo investigate the analgesic effects of transversus abdominis plane (TAP) block in conjunction with paracetamol and ibuprofen in patients undergoing laparoscopic colonic resection. DESIGNRandomised placebo-controlled double-blind study. SETTINGHerlev University Hospital, Copenhagen, Denmark, from March 2010 to February 2013. PATIENTSEighty adult patients scheduled for elective laparoscopic colectomy. INTERVENTIONSBilateral TAP block with 20 ml of either ropivacaine or isotonic saline. MAIN OUTCOME MEASURESVisual analogue scale (VAS) pain scores (0 to 100 mm) while coughing at 6 h after surgery (primary outcome). Secondary outcomes were area under the curve pain scores (2 to 24 h) at rest and while coughing, 24-h morphine consumption and incidence of nausea and vomiting. RESULTSVAS pain scores at 6 h while coughing was not different between groups (median, interquartile range), TAP, 27 (11 to 45) mm vs. placebo, 33 (20 to 49) mm (P = 0.20). Total 24-h morphine consumption was reduced in the TAP block group vs. placebo group, 30 (15 to 41) mg vs. 43 (30 to 67) mg, respectively (P = 0.008). This difference was most pronounced in the first postoperative hours. The remaining outcomes did not differ between groups. CONCLUSIONTAP block used in combination with paracetamol and ibuprofen did not reduce pain after laparoscopic colonic surgery. However, we found a 30% reduction in opioid use, most marked in the early postoperative period. TRIAL REGISTRATIONwww.clinicaltrials.gov (NCT01418144).