Assessment of Postoperative Analgesic Drug Efficacy: Method of Data Analysis Is Critical.

BACKGROUND: Pain intensity ratings and opioid consumption (OC) are ubiquitous indicators of pain in postoperative trials of the efficacy of interventional procedures. Unfortunately, consensus on the appropriate statistical handling of these outcomes has not been reached. The aim of this article was, therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. METHODS: Data from a randomized, double-blind, placebo-controlled study investigating the analgesic efficacy of a regional anesthetic block following a major elective surgical procedure were analyzed. The original data included measurements of pain intensity (visual analog scale [VAS]) at rest and during coughing (VAS0/2/4/6/12/18/24 h) and OC0-6/0-24 h administered by patient-controlled analgesia. The statistical analyses included comparisons of discrete pain intensity scores (VAS0/2/4/6/12/18/24 h), summary measures of pain intensity ratings (area under the curve [AUC]-VAS0-6/0-24 h; mean VAS0-6/0-24 h), and OC0-6/0-24 h. Finally, the analyses also included an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC0-6/0-24 h). Also, estimation of effect size, generalized odds ratio of the individual analgesic outcome variables was performed. RESULTS: Sixty-one patients were included in the final data analysis. Discrete pain intensity ratings differed significantly between the treatment groups at specific postoperative time points, but appropriate correction for multiple comparisons eliminated some of these differences. AUC-VAS0-6 h differed significantly at rest and during coughing, while no difference was found for AUC-VAS0-24 h. In contrast, mean VAS0-6 h and VAS0-24 h differed significantly between treatment groups at rest and during coughing. OC0-6/0-24 h differed significantly between the treatment groups. Finally, also PIOC0-6/0-24 h differed significantly at rest and during coughing. CONCLUSIONS: Our analyses demonstrate that the applied statistical method may alter the statistical significance and estimates of effect size of analgesic outcome variables in postoperative pain trials. Our findings underline the importance of defining valid statistical methods for future analgesic drug trials. We propose an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC). The method combines two interdependent analgesic outcomes, lowers the risk of mass significance, and provides more accurate representation of the dynamic nature of postoperative pain and analgesic drug efficacy.

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

BACKGROUND: A key point in pathways for optimal rehabilitation and enhanced recovery is an effective postoperative multimodal pain treatment regimen. OBJECTIVE: To investigate the analgesic effects of transversus abdominis plane (TAP) block in conjunction with paracetamol and ibuprofen in patients undergoing laparoscopic colonic resection. DESIGN: Randomised placebo-controlled double-blind study. SETTING: Herlev University Hospital, Copenhagen, Denmark, from March 2010 to February 2013. PATIENTS: Eighty adult patients scheduled for elective laparoscopic colectomy. INTERVENTIONS: Bilateral TAP block with 20 ml of either ropivacaine or isotonic saline. MAIN OUTCOME MEASURES: Visual 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. RESULTS: VAS 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. CONCLUSION: TAP 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 REGISTRATION: www.clinicaltrials.gov (NCT01418144).

Atraumatic splenic rupture.

Atraumatic splenic rupture (AMR) is a life-threatening condition with a wide range of aetiologies, and it may present with a vague symptomatology. Therefore, AMR can be diagnostically challenging. In this review, we wish to focus on the fact that guidelines only exist for traumatic splenic rupture although they may be applicable for AMR too. In addition, a stringent ABCDE approach for clinical examination may early and reliable diagnose the patients and guide further imaging examination and treatment.

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.

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 χ(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.

Potentially toxic concentrations in blood of total ropivacaine after bilateral transversus abdominis plane blocks; a pharmacokinetic study.

CONTEXT: Elevated blood levels of lidocaine and ropivacaine have been described after transversus abdominis plane (TAP) block. OBJECTIVE: To investigate the pharmacokinetic profile of ropivacaine after bilateral TAP blocks. DESIGN: Prospective observational pharmacokinetic study. SETTING: University teaching hospital in Copenhagen, Denmark. PATIENTS: Twenty-one adult patients presenting for abdominopelvic surgery with bilateral TAP blocks were enrolled. PROCEDURES: Ultrasound-guided TAP blocks with bilateral injections of 20 ml ropivacaine 0.5% w/v (total dose 200 mg). Blood was sampled at 0, 10, 30 and 60 min after TAP blocks. MEASURES: Total and free peak blood concentrations (Cmax) of ropivacaine. RESULTS: Data were analysed from N = 18 patients. The median dose of ropivacaine was 2.7 mg kg(-1) (range: 1.9-4.2 mg kg(-1)). Median total ropivacaine concentrations were 1.0, 1.6 and 1.7 µg ml(-1) at 10, 30 and 60 min, respectively. Six patients (33%) had Cmax values above 2.2 µg ml(-1) and the highest concentration measured was 5.1 µg ml(-1). One patient had a 33% drop in mean arterial blood pressure. CONCLUSION: TAP blocks with bilateral injections of 20 ml ropivacaine 0.5% w/v gave rise to potentially toxic peak blood concentrations of total ropivacaine in one-third of the patients.

Effective dermatomal blockade after subcostal transversus abdominis plane block.

INTRODUCTION: The ultrasound-guided transversus abdominis plane (TAP) block is used to treat postoperative pain after abdominal surgery. Abdominal wall sensory nerves are anaesthetised by injecting local anaesthetics into the neurofascial plane between the internal oblique and the transversus abdominis muscles. Sensory assessment of a TAP block may guide the decision on the extent of the block. The purpose of this study was to investigate if the dermatomal extent of sensory blockade after injection of 20 ml 0.5% ropivacaine bilaterally into the TAP can be assessed using cold and pinprick sensation. MATERIAL AND METHODS: Subcostal TAP block was performed bilaterally in 20 awake patients scheduled for elective abdominal surgery. Sensory change in dermatomes T4-L4 was tested with pinprick using a blunt needle and cold disinfectant swabs after 10, 20 and 30 minutes. RESULTS: Data from 20 patients (40 blocks) were analysed. Eighteen patients registered sensory change after subcostal TAP block, and dermatomes T10-T12 were blocked after 30 minutes in all of these patients. Spread of sensory change to dermatomes T5-L3 was variable. CONCLUSION: This study confirmed that the dermatomal extent of a sensory blockade after a single-shot subcostal TAP block can be assessed using cold and pinprick sensation. FUNDING: not relevant. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov with the registration number NCT01024868.