Timing of ibuprofen use and bone mineral density adaptations to exercise training

Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti‐inflammatory drugs (NSAIDs) blocks the bone‐formation response to loading when administered before, but not immediately after, loading. The aim of this proof‐of‐concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n = 73) aged 21 to 40 years completed a supervised 9‐month weight‐bearing exercise training program. They were randomized to take (1) ibuprofen (400 mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi‐W dual‐energy X‐ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n = 17; PLAC/PLAC, n = 23; and PLAC/IBUP, n = 14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p < .001; neck, p = .026; trochanter, p = .040; shaft, p = .019) but not the spine (p = .242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total‐hip BMD changes averaged –0.2% ± 1.3%, 0.4% ± 1.8%, and 2.1% ± 1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response. © 2010 American Society for Bone and Mineral Research     

Postoperative analgesia with preoperative oral ibuprofen or acetaminophen in children undergoing myringotomy

Previous studies have shown over 70% of children require analgesics following bilateral myringotomy and tube placement (BM&T). This double-blind, placebo-controlled study compared the postoperative analgesic effects of preoperatively administered oral acetaminophen or ibuprofen. Forty three ASA I or II children age six months or older scheduled for elective BM&T were randomized to receive acetaminophen (paracetamol) 15 mg·kg⁻¹, ibuprofen 10 mg·kg⁻¹, or placebo. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) upon arrival to the PACU and at 5, 10, 15, 30, 45, and 60 min. CHEOP scores did not differ between the groups at any time. There was no difference in the number of children receiving rescue analgesia. This study showed no benefit of preoperatively administered oral ibuprofen 10 mg·kg⁻¹ or acetaminophen 15 mg·kg⁻¹ over placebo for the relief of postoperative pain in children undergoing BM&T.     

Ibuprofen in the treatment of postoperative pain in small children. A randomized double–blindplacebo controlled parallel group study

The efficacy of ibuprofen as a pre–emptive analgesic for postoperative pain was investigated in 81 children in the age between one and four years subjected to elective surgery. The patients were randomized into two groups receiving rectally either ibuprofen 40 mgkg^-1 d^-1, divided into four equal doses, or placebo in a double blind manner. Additional pain relief was provided by morphine. In the recovery room ibuprofen provided superior pain relief during the first hour and significantly reduced the need of morphine. Heart rate and arterial blood pressure were lower in children who received ibuprofen, probably reflecting better analgesia. The side effects were mild and similar in both groups. We conclude that rectal ibuprofen is a safe analgesic in children in the age between 1 and 4 years and reduces the need of opioids for postoperative pain relief.     

The effect of dextromethorphan, alone or in combination with ibuprofen, on postoperative pain after minor gynaecological surgery

BACKGROUND: Experimental studies have demonstrated that peripheral tissue injury may lead to hyperexcitability of nociceptive neurones in the dorsal horn, in part mediated by N-methyl-D-aspartate (NMDA)-receptor mechanisms. Sensitisation of dorsal horn neurones may be an important contributor to postoperative pain. The aim of the present study was to investigate the effect of the NMDA-receptor antagonist dextromethorphan on pain after minor gynaecological surgery, and to evaluate a potential additive effect with ibuprofen. METHODS: In a double-blind, placebo-controlled study, 100 patients scheduled for elective termination of pregnancy were randomised to receive placebo, oral ibuprofen 400 mg, oral dextromethorphan 120 mg, or a combination of ibuprofen 400 mg and dextromethorphan 120 mg, 1 h before surgery. Pain and analgesic requirements were assessed 0.5, 1 and 2 h after operation. RESULTS: We observed no effect of dextromethorphan on visual analogue scale (VAS) pain scores or analgesic consumption, and no additive or synergistic analgesic effects between ibuprofen and dextromethorphan. Ibuprofen reduced pain scores compared with placebo, and analgesic consumption compared with both placebo and dextromethorphan. The combination of ibuprofen and dextromethorphan increased preoperative nausea compared with both placebo and ibuprofen, whereas no statistically significant side effects were observed with dextromethorphan alone. CONCLUSION: No analgesic effects of oral dextromethorphan 120 mg on pain after surgical termination of labour, and no additive analgesic effects when combined with ibuprofen 400 mg, were observed. Ibuprofen reduced both VAS pain scores and analgesic consumption compared with placebo.     

Intraoperative opioid dosing in children with and without cerebral palsy

Objective: To describe the differences in intraoperative opioid dosing and associated outcomes in children with and without cerebral palsy (CP). Background: Previous work on children with cognitive impairment has suggested that they receive less intraoperative opioid than children without cognitive impairment. This finding may be due to a common concern that impaired children are hypersensitive to the adverse effects of opioids. Patterns in intraoperative opioid dosing have yet to be studied in children with motor impairment (e.g. CP). Methods: We examined the medical records of pediatric patients with CP who underwent orthopedic surgery over the last decade at our institution, as well as the records of a randomly selected group of pediatric orthopedic patients without CP (non‐CP). Outcome variables were intraoperative opioid dosing, postoperative intensive care unit (ICU) admission, and postoperative oxygen desaturation. We collected demographic, surgical, and medical data for covariate analysis. A stepwise multivariate regression was used for each outcome. Results: Seventy‐one (71) CP and 77 non‐CP charts were included in the study. CP children received significantly less intraoperative opioid (3.26 ± 3.01 μg·kg^?1 fentanyl dose equivalents) than non‐CP children (4.58 ± 3.79 μg·kg^?1) (P = 0.02), and this difference was corroborated by the regression analysis, which significantly associated CP with decreased opioid dosing (P < 0.001). In addition, intraoperative opioid dosing, but not CP, predicted ICU admission (odds ratio: 1.463, 95% CI: 1.042–2.054, P = 0.03) and postoperative oxygen desaturation (odds ratio: 1.174, 95% CI: 1.031–1.338, P = 0.02). Conclusions: Similar to prior research on children with cognitive impairment, a reduction in intraoperative opioid dosing was found in children with CP. Given the discrepant doses of intraoperative opioid between groups, it is unclear whether children with CP are at any greater risk for untoward opioid‐related events.     

Enhanced recovery after surgery in children: Promising,evidence‐based multidisciplinary care

Enhanced recovery after surgery (ERAS) is a multimodal approach to the care of the surgical patient focused on reducing the stress response and associated physiologic changes that accompany surgery. Over the past 20 years, ERAS programs have been found to result in reduced LOS and complications in adult patients. Despite abundant adult literature describing implementation and outcomes of enhanced recovery programs, pediatric data in this area is sparse. This educational review describes the history and elements of ERAS protocols, reviews the available evidence in adult and pediatric populations, compares and contrasts ERAS with the PSH, and offers strategies for implementation and ideas for future directions of ERAS in children.     

Analgesic efficacy of rectal acetaminophen and ibuprofen alone or in combination for paediatric day-case adenoidectomy

Background. Acetaminophen and non-steroidal anti-inflammatorydrugs have different mechanisms of action. We investigated ifcombining rectal acetaminophen with ibuprofen would providebetter postoperative analgesia compared with either drug aloneafter adenoidectomy in children. Methods. 160 children, aged 1–6 yr, undergoing day-caseadenoidectomy, were randomized to receive either acetaminophen40 mg kg^–1, ibuprofen 15 mg kg^–1, their combination,or placebo rectally immediately after anaesthetic induction.A standard anaesthetic method was used and all children receivedalfentanil 10 µg kg^–1 i.v. during induction. Meperidine5–10 mg i.v. was used for rescue analgesia for a painscore (Objective Pain Scale) over 3. Recovery times, sedationscores and the need for rescue analgesia and adverse eventsduring the first 24 h after anaesthesia were recorded. Rescueanalgesic at home was ibuprofen 10 mg kg^–1. Results. Total meperidine requirements were significantly lessin the groups receiving acetaminophen, ibuprofen, or their combinationcompared with the group receiving placebo indicating an opioid-sparingeffect of 19–28% (P<0.05). Children given acetaminophenwere more sedated than those given ibuprofen (P<0.05). Dischargecriteria were fulfilled earlier in the ibuprofen group thanin all the other groups (P<0.05). At home, less children(49%) needed rescue analgesia in the combination group comparedwith the other groups (74–77%) (P<0.02). Conclusions. We conclude that prophylactically administeredrectal acetaminophen combined with ibuprofen does not improveanalgesia after adenoidectomy in the immediate postoperativeperiod compared with either drug alone but does decrease theneed for analgesia at home. Ibuprofen results in lesser sedationand faster discharge than when acetaminophen is used. Br J Anaesth 2003; 91: 363–7     

Non-steroidal anti-inflammatory drug use and the risk of benign prostatic hyperplasia-related outcomes and nocturia in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Study Type – Therapy (cohort) Level of Evidence 4 What's known on the subject? and What does the study add? Accumulating evidence suggests that inflammation may contribute to the development of BPH and LUTS. Therefore, it is plausible that anti‐inflammatory agents, such as aspirin and other NSAIDs, may reduce the risk of BPH/LUTS, as was observed in a recent analysis of daily aspirin use and BPH/LUTS risk in the Olmsted County Study of Urinary Symptoms and Health Status in Men. The present study, conducted in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, found no association for recent aspirin or ibuprofen use with the risk of BPH/LUTS.

OBJECTIVE

• ? To investigate the relationship between non‐steroidal anti‐inflammatory drug (NSAID) use and the incidence of benign prostatic hyperplasia (BPH)‐related outcomes and nocturia, a lower urinary tract symptom (LUTS) of BPH, in light of accumulating evidence suggesting a role for inflammation in BPH/LUTS development.

PATIENTS AND METHODS

• ? At baseline, participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial completed questions on recent, regular aspirin and ibuprofen use, BPH surgery, diagnosis of an enlarged prostate/BPH, and nocturia. Participants in the intervention arm also underwent a digital rectal examination (DRE), from which prostate dimensions were estimated, as well as a prostate‐specific antigen (PSA) test. Only participants in the intervention arm without BPH/LUTS at baseline were included in the analysis (n= 4771).
• ? During follow‐up, participants underwent annual DREs and PSA tests, provided annual information on finasteride use, and completed a supplemental questionnaire in 2006–2008 that included additional questions on diagnosis of an enlarged prostate/BPH and nocturia.
• ? Information collected was used to investigate regular aspirin or ibuprofen use in relation to the incidence of six BPH/LUTS definitions: diagnosis of an enlarged prostate/BPH, nocturia (waking two or more times per night to urinate), finasteride use, any self‐reported BPH/LUTS, prostate enlargement (estimated prostate volume ≥30 mL on any follow‐up DRE) and elevation in PSA level (>1.4 ng/mL on any follow‐up PSA test).

RESULTS

• ? Generally, null results were observed for any recent, regular aspirin or ibuprofen use (risk ratio = 0.92–1.21, P= 0.043–0.91) and frequency of use (risk ratios for one category increase in NSAID use = 0.98–1.11, P‐trends = 0.10–0.99) with incident BPH/LUTS.

CONCLUSION

• ? The findings obtained in the present study do not support a protective role for recent NSAID use in BPH/LUTS development.

     

The efficacy of morphine and Entonox analgesia during chest drain removal in children

BACKGROUND: Morphine is commonly used for chest drain removal pain, although a few studies in adults suggest that inhalation agents may be effective for this procedure. Little is known about chest drain removal pain and its management in children. METHODS: Three separate studies were carried out at a large tertiary pediatric hospital to examine the characteristics and management of chest drain removal pain in children. Study 1 examined the prevalence and clinical characteristics of pain and analgesic practices in 135 nonventilated children aged 1 week to 18 years having chest drains removed. Study 2 was an observation study to determine the efficacy and safety of self-administered Entonox (50% nitrous oxide and oxygen) for chest drain removal pain in 30 children aged 7-18 years. Study 3 was a pilot randomized controlled trial comparing intravenous morphine and continuous flow Entonox for chest drain removal pain in 14 children aged 3.5 months to 2.75 years. RESULTS: In study 1, the prevalence of moderate to severe pain during chest drain removal was 76%. Morphine was commonly given preprocedure, but the dose varied considerably. In study 2, children experienced a significant increase in pain during the procedure compared with preprocedure pain at rest, despite receiving Entonox, morphine and/or diclofenac. However, procedure pain was no worse than preprocedure pain during movement or deep breathing. A few minor side effects occurred, which resolved spontaneously. In study 3, no differences were found in pain between the two treatment groups. Children experienced moderate to severe pain during the procedure, despite receiving Entonox or morphine. CONCLUSIONS: Morphine or Entonox alone are unlikely to provide adequate analgesia for chest drain removal pain in children. More research is needed to determine the most effective interventions for this procedure.     

Diclofenac and flurbiprofen with or without clonidine for postoperative analgesia in children undergoing elective ophthalmological surgery

We conducted a prospective, randomized study to compare the efficacy of preoperative diclofenac, flurbiprofen, and clonidine, given alone, as well as the combination of diclofenac and clonidine, and flurbiprofen and clonidine in controlling postoperative pain in 125 children. The patients (ASA I, 2-12 years) undergoing elective ophthalmological surgery were allocated to one of five groups: rectal diclofenac 2 mg.kg(-1) following oral placebo premedication, i. v. flurbiprofen 1 mg.kg(-1) following placebo premedication, oral clonidine premedication, rectal diclofenac 2 mg.kg(-1) following clonidine, and i.v. flurbiprofen 1 mg.kg(-1) following clonidine. The children received clonidine (4 microg.kg(-1)) or placebo 105 min before anaesthesia. Diclofenac or flurbiprofen was given immediately after induction of anaesthesia. Anaesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using a modified objective pain scale (OPS). No opioids were administered throughout the study. Rectal diclofenac 2 mg.kg(-1) i.v. flurbiprofen 1 mg.kg(-1), oral clonidine 4 microg.kg(-1) provided similar OPS scores and requirement for supplementary analgesics during 12 h after surgery. Combination of oral clonidine and one of these nonsteroidal analgesics minimized postoperative pain. Our findings suggest that this combined regimen may be a promising prophylactic approach to postoperative pain control in children undergoing ophthalmological surgery.