Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants

BACKGROUND: The safety and value of acetaminophen (paracetamol) in additionto continuous morphine infusion has never been studied in newbornsand young infants. We investigated the addition of acetaminophento evaluate whether it decreased morphine consumption in thisage group after major thoracic (non-cardiac) or abdominal surgery. METHODS: A randomized controlled trial was performed in 71 patients giveneither acetaminophen 90–100 mg kg^–1 day^–1orplacebo rectally, in addition to a morphine loading dose of100 µg kg^–1 and 5–10 µg kg^–1h^–1 continuous infusion. Analgesic efficacy was assessedusing Visual Analogue Scale (VAS) and COMFORT scores. Extramorphine was administered if VAS was 4. RESULTS: We analysed data of 54 patients, of whom 29 received acetaminophenand 25 received placebo. Median (25–75th percentile) agewas 0 (0–2) months. Additional morphine bolus requirementsand increases in continuous morphine infusion were similar inboth groups (P = 0.366 and P = 0.06, respectively). There wasno significant difference in total morphine consumption, respectively,7.91 (6.59–14.02) and 7.19 (5.45–12.06) µg kg^–1 h^–1for the acetaminophen and placebo group (P = 0.60). COMFORT[median (25–75th percentile) acetaminophen 10 (9–12)and placebo 11 (9–13)] and VAS [median (25–75thpercentile) acetaminophen 0.0 (0.0–0.2) and placebo 0.0(0.0–0.3)] scores did not differ between acetaminophenand placebo group (P = 0.06 and P = 0.73, respectively). CONCLUSIONS: Acetaminophen, as an adjuvant to continuous morphine infusion,does not have an additional analgesic effect and should notbe considered as standard of care in young infants, 0–2months of age, after major thoracic (non-cardiac) or abdominalsurgery.     

Preventive effects of perioperative parecoxib on post-discectomy pain

BACKGROUND: Cyclooxygenase inhibitor treatment is viewed increasingly critical because of safety considerations, and there are several open questions on their optimal use. METHODS: In a randomized placebo-controlled study in 320 patients undergoing discectomy, we administered parecoxib 40 mg either perioperatively (before operation and after operation), after operation (first dose given in the evening after surgery), or before operation (single parecoxib dose given 45 min before surgery). We measured the main outcome variables: average pain score, morphine consumption, and opioid-related symptom distress at 25, 49, and 73 h after surgery. RESULTS: Perioperative parecoxib significantly (i) improved the pain score compared with both placebo and postoperative parecoxib, (ii) decreased morphine consumption, and (iii) reduced the opioid-related symptom distress score. Neither a single preoperative dose nor postoperative parecoxib (first dose given in the evening after surgery) significantly improved morphine's analgesic effectiveness. CONCLUSIONS: Perioperative parecoxib compared with postoperative parecoxib improves post-discectomy pain and results in a reduction in adverse effects associated with opioid therapy. Postoperative parecoxib, or a single pre-incisional parecoxib dose, does not significantly improve post-discectomy pain or opioid side-effects up to 3 days after surgery.     

Advances in analgesia in the older patient

The average age of the world's population is increasing rapidly, with those over 80 years of age the fastest growing subsection of older persons. Consequently, a higher proportion of those presenting for surgery in the future will be older, including greater numbers aged over 100 years. Management of postoperative pain in these patients can be complicated by factors such as age and disease-related changes in physiology, and disease-drug and drug-drug interactions. There are also variations in pain perception and ways in which pain should be assessed, including in patients with cognitive impairment. Alterations in pharmacokinetics and pharmacodynamics may influence drugs and techniques used for pain relief. The evidence-base for postoperative pain management in the older population remains limited. However, most commonly used analgesic regimens are suitable for older patients if adapted and titrated appropriately.     

Iontophoretic transdermal system using fentanyl compared with patient-controlled intravenous analgesia using morphine for postoperative pain management

Background: The fentanyl iontophoretic transdermal system (fentanyl ITS)enables needle-free, patient-controlled analgesia for postoperativepain management. This study compared the efficacy, safety, andease of care of fentanyl ITS with patient-controlled, i.v. analgesia(PCIA) with morphine for postoperative pain management. Methods: A prospective, randomized, multicentre trial enrolled patientsin Europe after abdominal or orthopaedic surgery. Patients receivedfentanyl ITS (n = 325; 40.0 µg fentanyl over 10 min) ormorphine PCIA [n = 335; bolus doses (standard at each hospital)]for 72 h. Supplemental i.v. morphine was available during thefirst 3 h. The primary efficacy measure was the patient globalassessment (PGA) of the pain control method during the first24 h. Results: PGA ratings of ‘good’ or ‘excellent’were reported by 86.2 and 87.5% of patients using fentanyl ITSor morphine PCIA, respectively (95% CI, –6.5 to 3.9%).Mean (SD) last pain intensity scores (numerical rating scale,0–10) were 1.8 (1.77) and 1.9 (1.86) in the fentanyl ITSand morphine PCIA groups, respectively (95% CI, –0.38to 0.18). More patients reported a system-related problem forfentanyl ITS than morphine PCIA (51.1 vs 17.9%, respectively).However, fewer of these problems interrupted pain control (4.4vs 41.3%, respectively). Patients, nurses, and physiotherapistsreported more favourable overall ease-of-care ratings for fentanylITS than morphine PCIA. Study termination rates and opioid-relatedside-effects were similar between groups. Conclusion: Fentanyl ITS and morphine PCIA were comparably effective andsafe.     

Effect of combining dexmedetomidine and morphine for intravenous patient-controlled analgesia

Background: Perioperative use of dexmedetomidine is associated with reductionin postoperative analgesic requirements. This study examinedwhether dexmedetomidine added to i.v. patient-controlled analgesia(PCA) morphine could improve analgesia while reducing opioid-relatedside-effects. Methods: In this double-blinded, randomized, controlled study, 100 womenundergoing abdominal total hysterectomy were allocated to receiveeither morphine 1 mg ml^–1 alone (Group M) or morphine1 mg ml^–1 plus dexmedetomidine 5 µg ml^–1 (GroupD) for postoperative i.v. PCA, which was programmed to deliver1 ml per demand with a 5 min lockout interval and no backgroundinfusion. Cumulative PCA requirements, pain intensities, cardiovascularand respiratory variables, and PCA-related adverse events wererecorded for 24 h after operation. Results: Compared with Group M, patients in Group D required 29% lessmorphine during the 0–24 h postoperative period and reportedsignificantly lower pain levels from the second postoperativehour onwards and throughout the study. Whereas levels of sedationwere similar between the groups at each observational time point,decreases in heart rate and mean blood pressure from presurgerybaseline at 1, 2, and 4 h after operation were significantlygreater in Group D (by a range of 5–7 beats min^–1and 10–13%, respectively). The 4–24 h incidenceof nausea was significantly lower in Group D (34% vs 56.3%,P<0.05). There was no bradycardia, hypotension, oversedation,or respiratory depression. Conclusions: The addition of dexmedetomidine to i.v. PCA morphine resultedin superior analgesia, significant morphine sparing, less morphine-inducednausea, and was devoid of additional sedation and untoward haemodynamicchanges.     

Hormonal and metabolic stress responses after major surgery in children aged 0-3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphine

Children aged 0–3 yr were stratified for age and randomizedto receive either continuous morphine (CM, 10 µg kg^–1 h^–1)with three-hourly placebo boluses or intermittent morphine (IM,30 µg kg^–1 every 3 h) with a placeboinfusion for postoperative analgesia. Plasma concentrationsof epinephrine, norepinephrine, insulin, glucose and lactatewere measured before and at the end of surgery and 6, 12 and24 h after surgery. Pain was assessed with validated painscales [the COMFORT scale and a visual analogue scale (VAS)]with the availability of additional morphine doses. Minor differencesoccurred between the randomized treatment groups, the oldestIM group (aged 1–3 yr) having a higher blood glucoseconcentration (P=0.003), mean arterial pressure (P=0.02) andCOMFORT score (P=0.02) than the CM group. In the neonates, preoperativeplasma concentrations of norepinephrine (P=0.01) and lactate(P<0.001) were significantly higher, while the postoperativeplasma concentrations of epinephrine were significantly lower(P<0.001) and plasma concentrations of insulin significantlyhigher (P<0.005) than in the older age groups. Postoperativepain scores (P<0.003) and morphine consumption (P<0.001)were significantly lower in the neonates than in the older agegroups. Our results show that continuous infusion of morphinedoes not provide any major advantages over intermittent morphineboluses for postoperative analgesia in neonates and infants. Br J Anaesth 2001; 87: 390–9     

Pain management after adenoidectomy with ketoprofen: comparison of rectal and intravenous routes

We compared the efficacy of rectally and intravenously administeredketoprofen for pain management after day-case adenoidectomy.Patients (123 children aged 1–9 yr) were allocatedrandomly to receive on induction of anaesthesia ketoprofen 25 mgrectally with an i.v. placebo, ketoprofen 25 mg i.v. witha rectal placebo, or placebo both i.v. and rectally. The methodof anaesthesia and the operative technique were standardized.Postoperative pain was assessed at rest and during swallowingusing the Maunuksela pain scale (0=no pain, 10=worst possiblepain). Fentanyl 0.5 µg kg^–1 was givenas rescue analgesia. There was no significant difference betweenthe two ketoprofen groups in their requirement for rescue analgesics.However, both the proportion of children needing rescue analgesics[55 of 84 children (65%) vs. 33 of 39 children (84%); difference19%, 95% confidence interval 4–34%, P=0.029] and the numberof rescue analgesic doses [mean 1.2 (SD 1.2) vs. 2.2 (1.4);mean difference 0.9, 95% confidence interval 0.4–1.4,P=0.001] were significantly lower among children receiving ketoprofenthan in children receiving placebo. Adverse events, durationof operation, perioperative bleeding, pain scores and time ofdischarge were similar in the three groups. Br J Anaesth 2000; 85: 836–40     

Pre-incisional epidural ropivacaine, sufentanil, clonidine, and (S)+-ketamine does not provide pre-emptive analgesia in patients undergoing major pancreatic surgery

BACKGROUND: The concept of pre-emptive analgesia remains controversial. This prospective, randomized, and double-blind study compared epidural administration of ropivacaine 2 mg ml(-1), sufentanil 0.5 microg ml(-1), clonidine 3 microg ml(-1), and S(+)-ketamine 0.25 mg ml(-1) (study solution) given before incision with the same combination started at the end of the operation. METHODS: After testing the stability of the solution using high performance liquid chromatography (HPLC) and examining 12 patients for possible side-effects in comparison with the epidural infusion of ropivacaine 2 mg ml(-1) and sufentanil 0.5 microg ml(-1), 30 patients undergoing major pancreatic surgery were recruited into the study. Before induction of anaesthesia, an epidural catheter was inserted (TH6-8). Patients in Group 1 received a bolus of 8 ml followed by a continuous infusion (8 ml h(-1)) of the study solution before induction of anaesthesia. In Group 2, patients received the same volume of saline before operation, the study solution was started at the end of surgery. After operation, the infusion was maintained for at least 96 h using a patient-controlled epidural analgesia (PCEA) pump in both groups. Patients were evaluated up to the seventh postoperative day for pain and side-effects. RESULTS: Visual analogue scale (VAS) values at rest were as follows: G1 vs G2: 24 h, 19 (sd 23) vs 6 (13); 48 h, 4 (10) vs 11 (21); and 72 h, 12 (22) vs 13 (21). VAS values during coughing and mobilization were also comparable. Total volume of epidural infusion was 904 (114) ml in G1 vs 892 (154) ml in G2. The incidence of side-effects (nausea, vomiting, and motor block) was low and not different between the groups. CONCLUSIONS: Pre-incisional epidural analgesic infusion did not provide pre-emptive analgesia compared with administration started at the end of surgery, but both groups had low pain scores.     

Analgesic effects of parecoxib following total abdominal hysterectomy

Background. Forty-eight ASA I–II patients undergoing totalabdominal hysterectomy (TAH) were studied in a double blind,randomized placebo controlled trial of parecoxib for postoperativeanalgesia. Methods. All patients were given propofol 2–4 mg kg^–1i.v., a non-depolarizing muscle relaxant, morphine 10 mg i.v.and prochlorperazine 12.5 mg i.m. intraoperatively. Their lungswere ventilated with nitrous oxide and isoflurane 1–1.5%in oxygen. Morphine was self-administered for postoperativeanalgesia via a patient controlled analgesia (PCA) device. Patientswere allocated randomly to receive either parecoxib 40 mg i.v.or normal saline on induction of anaesthesia. Results. Twelve patients did not complete the study. Of theremaining 36 patients, there was no significant difference betweenthe treatment groups in age, weight, ASA status, duration ofsurgery, or intraoperative dose of morphine. However, mean (95%CI) 24 h morphine consumption of 54 (42–65) mg in theparecoxib group was significantly (P=0.04) lower than that of72 (58–86) mg in the placebo group. Pain intensity scoreson sitting up were significantly lower (P=0.02) in the parecoxibgroup compared with placebo. There was no significant differencebetween the treatment groups in pain intensity scores at restand on deep inspiration, or in nausea, total number of vomitingepisodes, median number of rescue antiemetic doses, and sedationscores. Conclusions. Parecoxib 40 mg i.v. may be recommended in patientshaving TAH as it provides morphine-sparing analgesia. Br J Anaesth 2003; 90: 746–9     

Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement

Background. The goal of this study was to evaluate the effectivenesson postoperative pain, and cognitive impact, of patient-controlledanalgesia (PCA) compared with subcutaneous (s.c.) injectionsof morphine in elderly patients undergoing total hip replacement(THR). Methods. Forty patients older than 70 yr were randomly assignedto two different postoperative analgesic techniques for 48 h:i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCAgroup) or regular s.c. morphine injections (SC group). Postoperativepain was assessed at rest and when moving, using a visual analoguescale (VAS) every 4 h. A Mini Mental Status (MMS) examinationwas used to assess cognitive functions before surgery, at 2h, 24 h and 48 h after surgery, and at hospital discharge. Side-effectswere also recorded systematically during the first 48 h aftersurgery. Results. The PCA group showed significantly lower pain scoresthan the SC group both at rest and during mobilization. However,the clinical significance of pain scores was weak. There wasno intergroup difference in postoperative MMS scores. The incidenceof side-effects was similar in both groups. Conclusions. We conclude that in healthy elderly subjects undergoingTHR, the flexibility of the analgesic regimen is more importantthan the route of administration with regard to efficacy, adverseeffects and recovery of cognitive function. Br J Anaesth 2003; 90: 53–7