Patient preference for route of diclofenac

The purpose of this study was to investigate whether patients attending an A&E department would prefer injection or suppository diclofenac as analgesia if oral medication was contraindicated. Patients presenting to the 'walking wounded' side were asked to fill in a questionnaire indicating their preference. The results showed a strong preference for intramuscular diclofenac. If we wish to prescribe rectal diclofenac, we should be prepared to take into account the patient's wishes first and, if necessary, explain our reasoning.     

Oral or rectal diclofenac for laparoscopic sterilization

In the UK, perioperative non-steroidal anti-inflammatory drugs are commonly administered via the rectal route even though suppositories are unpopular with patients. This prospective, randomised, double-blind study compares the analgesic effectiveness of diclofenac 100 mg given either orally or rectally to 42 ASA grades 1 and 2 patients scheduled to undergo day-case laparoscopic sterilization by the application of Filshie clips. General anaesthesia was induced with fentanyl 2 μg kg⁻¹ and propofol and maintained with isoflurane and nitrous oxide in oxygen. No difference was observed between the two groups in postoperative pain scores, morphine requirement, nausea and vomiting rates and time to achievement of street fitness. One patient in the rectal group and none in the oral group required in-patient admission. We conclude that oral and rectal diclofenac are of equal effectiveness in this approach to day-case laparoscopic sterilization.     

Pre-operative analgesia with rectal diclofenac and/or paracetamol in children undergoing inguinal hernia repair

Both rectal diclofenac and paracetamol are commonly used to treat acute postoperative pain in children but combining them to improve the quality of analgesia is controversial. This study aimed to detect whether the pre-operative combined administration of rectal diclofenac and paracetamol is superior to either drug alone. One hundred and eight patients were randomly assigned to receive either rectal diclofenac 1 mg.kg⁻¹ or paracetamol 40 mg.kg⁻¹ or their combination 1 h prior to surgery. In the first 24 h postoperatively, pain was assessed using the Wong and Baker Pain Scale. If the patients experienced a pain score of 2 or more, morphine was given. The total dose of morphine and number of doses required were recorded. Children who received the rectal diclofenac-paracetamol combination experienced a lower pain scale and a decreased need for morphine compared with children receiving each drug alone.     

The effect of rectal diclofenac on pruritus in patients receiving intrathecal morphine

In this prospective randomised study, pruritus and pain were evaluated in patients undergoing abdominal surgery in which intrathecal morphine was administered. Each patient received intrathecal morphine 0.3 mg prior to induction, followed by a standard anaesthetic. The patients were randomly allocated to one of two groups. One group received 100 mg of rectal diclofenac immediately post-induction. Patients receiving diclofenac had significantly lower pruritus scores at 30 min (p = 0.0076), 2, 4, 8 and 24 h postoperatively, as well as significantly reduced pain scores at each time point (p < 0.0001 at each study interval). Morphine consumption in the first 24 h was also significantly lower in this group. In conclusion, rectal administration of diclofenac significantly reduces the incidence and severity of postoperative pruritus. It also significantly reduces pain and further analgesic requirements postoperatively.     

Rectal pH in children

In an attempt to establish normal values for rectal pH in children, we have measured pH in 100 paediatric patients. Measurement of rectal pH was performed in 25 infants and 75 children (27 girls and 73 boys) using a monocrystalline antimony electrode. Rectal pH was 9.6 +/- 0.9 (mean +/- SD, range 7.2 to 12.1) and was independent of sex, age and nutrition. This wide range of rectal pH values offers a possible explanation for the widely scattered bioavailability of drugs administered by the rectal route. Mean rectal pH was considerably higher than that reported for adults; this unexpected alkalinity should be taken into account, when drug formulations are considered for rectal administration in children.     

Preoperative rectal diclofenac versus paracetamol for tonsillectomy: effects on pain and blood loss

BACKGROUND: Diclofenac is widely used for postoperative analgesia but the perioperative safety of this drug is controversial because of its effect on platelet aggregation, which might increase blood loss. In a prospective investigator-blinded study the effects of diclofenac and paracetamol on pain and blood loss were compared in patients undergoing tonsillectomy. METHOD: Ninety patients were randomised to receive rectal diclofenac 0.65-1.0 mg x kg(-1) or paracetamol 13-20 mg x kg(-1) preoperatively. Ten patients were excluded after randomisation. Pain was evaluated postoperatively by means of the visual analogue scale and by recording the use of pethidine for rescue analgesia. Perioperative blood loss was estimated from measured intraoperative blood loss; use of drugs to achieve haemostasis, and the incidence of reoperations. RESULTS: Anaesthetic or surgical managements did not differ between the groups, but a significantly longer period of surgery was found in the diclofenac group, 32+/-16 vs. 25+/-11 min (P = 0.024). Pain scores or pethidine consumption were not significantly different between the groups. Intraoperative blood loss was significantly larger in the diclofenac group, 1.9 (1.1-3.1) vs. 1.1 (0.7-2.0) ml x kg(-1) (P = 0.007). CONCLUSION: Preoperative rectal diclofenac offers no advantage over paracetamol with respect to postoperative analgesia in tonsillectomy patients but increases intraoperative blood loss.     

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.     

The effect of paracetamol or diclofenac administered before operation on postoperative pain and behaviour after adenoidectomy in small children

We compared the effects of rectally administered diclofenac (12.5 mg) with paracetamol (125 mg) on pre- and postoperative behaviour and the need for supplementary analgesia in 44 children scheduled for adenoidectomy (with or without myringotomy). The study drugs were given in combination with diazepam (0.5 mg.kg-1) about 20 min before the children were taken to the operating theatre. On arrival there, the children who had received diclofenac were significantly quieter (< 0.05), easier to handle (p < 0.01) and cried less (p < 0.05) than those in the paracetamol group. During recovery, children in the diclofenac group needed fewer supplementary doses of intravenous pethidine than those receiving paracetamol (p < 0.001). There were no obvious differences between the groups in intra-operative bleeding (as estimated by the surgeon), or in measured blood loss. No postoperative complications became evident. The pre-operative rectal administration of diclofenac for pain relief after adenotomy is safe and effective.     

Persistently high plasma morphine-6-glucuronide levels despite decreased hourly patient-controlled analgesia morphine use after single-dose diclofenac: potential for opioid-related toxicity.

We studied the time course of clinical and pharmacokinetic effects after the rectal administration of diclofenac 100 mg in seven patients using patient-controlled morphine (PCA) on the first postoperative day after major spinal surgery. Plots of plasma diclofenac concentrations and pain intensity difference (PID) demonstrated counterclockwise hysteresis consistent with distribution to a central effect compartment such as the central nervous system. Mean +/- SEM (range) maximum PID and its timing were 62%+/-10% (32%-98%) and 309+/-20 (210-360) min after the administration of diclofenac, respectively. Minimal respiratory rates were significantly slower after the administration of diclofenac (P < 0.001), occurring at 197+/-51.9 (60-360) min; arterial desaturations occurred in two patients without oxygen therapy. Plasma morphine and morphine-6-glucuronide (M6G) concentrations interpolated to the average time of minimal respiratory rate indicated decreases of 23%+/-13% (0%-79%) and 1%+/-9% (0%-32%) from their respective starting values. Plasma M6G concentrations were significantly different from baseline only 420 and 480 min after the administration of diclofenac. The potential opioid-sparing effects of a nonsteroidal antiinflammatory drug added during PCA morphine use may not be manifest for several hours. During this lag, plasma concentrations of M6G may reach and remain at levels high enough to increase the risk of respiratory depression and other opioid side effects for hours. IMPLICATIONS: Plasma concentrations of morphine, morphine-6-glucuronide, and diclofenac were measured postoperatively after a single dose of rectal diclofenac 100 mg was added to morphine patient-controlled analgesia. Peak analgesia occurred 309 min and respiratory depression 197 min after diclofenac administration. Morphine consumption had decreased by 20%, but concentrations of the active metabolite morphine-6-glucuronide were unchanged. Vigilance is recommended in patients receiving patient-controlled analgesia opioids and nonsteroidal antiinflammatory drugs.     

Comparison of the effect of diclofenac with hyoscine-N-butylbromide in the symptomatic treatment of acute biliary colic

BACKGROUND: Although non-steroidal anti-inflammatory drugs (NSAID) and spasmolytics have been used to relieve biliary colic, the role of these drugs in the natural history of biliary colic has not been clarified. The objective of the present study is to compare the efficacy of intramuscular diclofenac with intramuscular hyoscine in the treatment of pain of acute biliary colic, and to study their role in the natural history of biliary colic and in the prevention of cholelithiasis-related complications. METHODS: Seventy-two consecutive patients with biliary colic were enrolled in this prospective, randomized, double-blind study. They received either a single 75 mg intramuscular dose of diclofenac (n = 36) or similarly administered 20 mg of hyoscine (n = 36). Pain severity was recorded on a visual analogue scale 30 min, 1 h, 2 h and 4 h after injection of the drug. Patients were then followed closely for the next 72 h for persistence or relapse of pain, or development of acute cholecystitis, or drug related complications. RESULTS: Diclofenac provided much more rapid relief of pain than hyoscine, as shown by significantly lesser pain scores after injection of the drug. 91.7% of patients on diclofenac were completely relieved of pain at 4 h as compared to 69.4% with hyoscine (P = 0.037). Progression to acute cholecystitis was seen in only 16.66% of patients on diclofenac as compared to 52.77% on hyoscine (P = 0.003). CONCLUSIONS: In patients with biliary colic, diclofenac gives much faster and more effective pain relief in a significantly larger number of patients as compared with hyoscine. Most remarkably, diclofenac can prevent progression of biliary colic to acute cholecystitis in a significant number of patients.     

Intravenous diclofenac sodium Does its administration before operation suppress postoperative pain?

Intravenous diclofenac sodium was evaluated in a double-blind randomised trial relative to intramuscular diclofenac, intravenous fentanyl, and intramuscular placebo in 160 patients undergoing extraction of impacted lower third molar teeth. The test drug was administered before operation in an attempt to alleviate postoperative pain. A 10-cm visual analogue scale was used to assess pain at 30 minutes and one day after surgery, if the patients stayed overnight. Patients who received intravenous diclofenac had significantly less pain than the other groups 30 minutes after operation. They also had significantly less pain one day after surgery than the placebo or opioid groups, but not less than the intramuscular diclofenac group. Capillary bleeding time, in comparison with placebo, was significantly prolonged after the use of intramuscular diclofenac, and a similar but nonsignificant trend was observed in the intravenous diclofenac group. No problems were encountered with excessive bleeding in any group.     

The pharmacokinetics and analgesic efficacy of larger dose rectal acetaminophen (40 mg/kg) in adults: a double-blinded, randomized study

Analgesic acetaminophen plasma concentrations are not known. We investigated in a randomized, double-blinded study the pharmacokinetics and analgesic efficacy of small- (AS; 20 mg. kg(-1)) and larger- (AL; 40 mg/kg) dose rectal acetaminophen and compared it with the combination (C) of rectal diclofenac (100 mg) and acetaminophen (20 mg/kg) in 65 women undergoing hysterectomy. Suppositories were administered after the induction of a standardized general anesthesia. Pain (measured by using a 10-cm visual analog scale) and morphine consumption (patient-controlled analgesia) were repeatedly assessed for 24 h. Acetaminophen plasma concentrations were measured by using a fluorescence polarization immunoassay. Antipyretic plasma concentrations (10-20 mg/L) after 40 mg/kg acetaminophen were not associated with improved analgesia or decreased opioid requirements; 20 mg/kg acetaminophen produced subtherapeutic plasma levels (<10 mg/L). Maximal plasma concentrations of 17.2 and 10.4 mg/L (P < 0.01, analysis of variance) were achieved after 4.2 and 3.6 h for the AL and AS groups, respectively. The only difference in clinical outcome was lower visual analog scale scores after acetaminophen/diclofenac (C 2.0 versus AS 3.2 and AL 3.4) 4 h after the induction (P < 0.05, analysis of variance). Acetaminophen pharmacokinetics in adults were similar to those observed in children. Analgesic plasma concentrations are likely to be higher than antipyretic plasma levels, which were only attained after twice the recommended rectal dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis. IMPLICATIONS: Acetaminophen pharmacokinetics were comparable in adults and children. Plasma concentrations known to reduce fever did not produce better pain relief and were only achieved after twice the conventional dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.     

Intramuscular application of diclofenac--case report and critical consideration of a therapeutic measure

Diclofenac is a non-steroidal anti-inflammatory drug of the phenylacetic class. It is frequently given as an intramuscular injection. However several, sometimes severe, side effects have been described after an i.m. administration. Based on a short case report about a fatal complication in the context of the i.m. administration of diclofenac, the arguments for and against the intramuscular injection of the drug are critically discussed. As a result, the administration of diclofenac as an intramuscular injection should be critically reviewed and alternatives -- as suppositories are available -- should be taken into account.     

Effect of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation.

Ninety-six women undergoing laparoscopic tubal ligation were randomized to receive intravenously either 0.2 or 0.4 microgram/kg of dexmedetomidine, 60 micrograms/kg of oxycodone, or 250 micrograms/kg of diclofenac for postoperative pain in a double-blind study design. The study drugs were administered in the recovery room for moderate or severe pain and were repeated until pain subsided or disappeared. In the group receiving diclofenac, 83% of the patients required analgesic supplementation with morphine. This contrasted (P less than 0.01) with 33% of the patients receiving either oxycodone or the higher dose of dexmedetomidine. After the first dose of oxycodone was injected, the visual analogue scale for pain (0%-100%) was reduced from 58% to 33%, whereas corresponding pain relief was only achieved after the third injection of 0.4 microgram/kg of dexmedetomidine. Repeated doses of 0.2 microgram/kg of diclofenac or dexmedetomidine did not reduce the visual analogue scale value by more than 17%. More sedation was seen with the higher dose of dexmedetomidine than with either diclofenac or oxycodone (P less than 0.001). Both doses of dexmedetomidine decreased heart rate when compared with diclofenac (P less than 0.001). In the group given 0.4 microgram/kg of dexmedetomidine, 33% of the patients required atropine for bradycardia. The authors conclude that after laparoscopic tubal ligation, intravenously administered dexmedetomidine relieves pain and reduces opioid drug requirement but is attended by sedation and a high incidence of bradycardia.     

Medication errors--new approaches to prevention

Medication errors in pediatric anesthesia represent an important risk to children. Concerted action to reduce harm from this cause is overdue. An understanding of the genesis of avoidable adverse drug events may facilitate the development of effective countermeasures to the events or their effects. Errors include those involving the automatic system of cognition and those involving the reflective system. Errors and violations are distinct, but violations often predispose to error. The system of medication administration is complex, and many aspects of it are conducive to error. Evidence-based practices to reduce the risk of medication error in general include those encompassed by the following recommendations: systematic countermeasures should be used to decrease the number of drug administration errors in anesthesia; the label on any drug ampoule or syringe should be read carefully before a drug is drawn up or injected; the legibility and contents of labels on ampoules and syringes should be optimized according to agreed standards; syringes should always be labeled; formal organization of drug drawers and workspaces should be used; labels should be checked with a second person or a device before a drug is drawn up or administered. Dosage errors are particularly common in pediatric patients. Causes that should be addressed include a lack of pediatric formulations and/or presentations of medication that necessitates dilution before administration or the use of intravenous formulations for oral administration in children, a frequent failure to obtain accurate weights for patients and a paucity of pharmacokinetic and pharmacodynamic data. Technological innovations, including the use of bar codes and various cognitive aids, may facilitate compliance with these recommendations. Improved medication safety requires a system-wide strategy standardized at least to the level of the institution; it is the responsibility of institutional leadership to introduce such strategies and of individual practitioners to engage in them.     

Rectal paracetamol has a significant morphine-sparing effect after hysterectomy

We have evaluated the morphine-sparing effect of rectal paracetamol during the first 24 h after abdominal hysterectomy in a placebo- controlled, double-blind study. We studied 72 patients receiving patient-controlled analgesia (PCA) with i.v. morphine after a standardized anaesthetic, allocated randomly to receive rectal paracetamol 1.3 g, diclofenac 50 mg or placebo, after wound closure and at 8 and 16 h. Suppositories were blinded by the hospital pharmacy. Study violations excluded data from seven patients. Patient data, morphine doses during anaesthesia and recovery, and sedation and nausea scores were comparable. Mean morphine consumption during PCA was 35.0 (SD 20.4) mg, 32.7 (27.4) mg and 54.9 (28.3) mg in the paracetamol (n = 24), diclofenac (n = 20) and placebo (n = 21) groups, respectively (P < 0.05). Morphine sparing during PCA for paracetamol and diclofenac (36% vs 40% over 24 h) was significant from 4 h. Global scores of average pain over 24 h were lower after diclofenac compared with paracetamol (P < 0.01) and placebo (P = 0.08). We conclude that rectal paracetamol was an efficacious adjuvant analgesic after regular dosing.      

Ketamine

Ketamine is an intravenous drug with special properties that make it the only agent that presently serves as anesthetic, sedative, amnesiac and analgesic. Although it is sometimes forgotten, ketamine is still considered a viable drug. Water soluble, stable and non-irritant when administered intravenously, ketamine has rapid onset after intravenous injection and provides acceptable anesthesia when administered in continuous infusion. There properties make ketamine useful for total intravenous anesthesia. Both propofol and midazolam are effective in reducing ketamine's adverse side effects. Administered in children by oral, nasal, rectal and intramuscular routes, ketamine allows for gentle anesthetic induction. It can also serve as an adjuvant in regional anesthesia to supplement analgesia. In adults ketamine is most often used for major surgery, particularly in the elderly or in high risk patients who are in shock, severely dehydrated or hemodynamically unstable, or in obstetric patients with hypovolemia or hemorrhage. It is probably the anesthetic of choice for patients with hyperreactive airways. Ketamine's strong analgesic effect at subanesthetic doses allows it to be used as an analgesic during postoperative intensive care or as an analgesic-plus-sedative for patients receiving mechanical ventilation. Interest in using ketamine at low doses for cancer and non-cancer patients with chronic pain has grown recently.     

Ondansetron versus diclofenac sodium in the treatment of acute ureteral colic: A double blind controlled trial

The aim of this study is to compare the effectiveness of the 5-HT₃ antagonist, ondansetron and a non-steroidal anti-inflammatory agent, diclofenac sodium, as a pain reliever in the treatment of acute ureteral colic. Sixty four patients with severe or moderate pain who were clinically diagnosed as having ureteral colic associated with microscopic or gross hematuria were included in the study. Thirty three patients were administered ondansetron and 31 patients were administered diclofenac sodium. Exclusion critera were known kidney or liver disease causing dysfunction, known hypersensitivity to ondansetron or diclofenac sodium, pregnancy, lactation, duodenal ulcer or bleeding. After pain assessment with a verbal scale and a visual analog scale (VAS), we randomized patients and administered 8 mg ondansetron intravenously to 33 patients and 75 mg diclofenac sodium intramuscularly to 31 patients and pain scores were recorded every 15 minutes. If significant pain relief was not achieved within 60 minutes, IV meperidine was given as rescue pain medication. Ondansetron was effective as a primary pain reliever in 14 (42.4%) patients, whereas 19 patients required additional medication. Diclofenac sodium was effective as a primary pain reliever in 24 (77.4%) patients, whereas 7 patients required additional medication. Ondansetron was not superior to diclofenac sodium in relieving pain in patients with acute ureteral colic.     

Paediatric postoperative analgesia A comparison of rectal diclofenac with caudal bupivacaine after inguinal herniotomy

Forty-three children for day case inguinal herniotomy under general anaesthesia were assigned randomly to receive either 1 ml/kg caudal bupivacaine 0.25% or rectal diclofenac 0.25 mg/kg intra-operatively to provide postoperative analgesia. Pain and demeanour were assessed by an observer in the early postoperative period after operation and by questionnaire for the parents over the first 24 hours. Caudal bupivacaine provided more pain-free patients at first but later the incidence of pain was similar in the two treatment groups. Rectal diclofenac is a useful alternative to caudal blockade in this group of patients.     

Hypoxic brain damage after intramuscular self-injection of diclofenac for acute back pain

We present a case of hypoxic brain damage that occurred after intramuscular injection of diclofenac due to a severe anaphylactic reaction. A 38-year-old nurse treated herself for acute lower back pain with 100 mg diclofenac intramuscularly. Five minutes later, she collapsed and developed coma and respiratory arrest. After cardiopulmonary resuscitation she was transferred to hospital. On admission she was comatose and received controlled ventilation of the lungs. Magnetic resonance imaging and computerized tomography showed signs of hypoxic brain injury and the patient died from central cardiopulmonary failure 7 days later. Intramuscular treatment with non-steroidal anti-inflammatory drugs such as diclofenac has rare but potentially severe side-effects. Therefore, intramuscular injections are inappropriate and should be replaced with oral or rectal treatment, which has similar absorption profiles.