Pain prevalence in hospitalized children: a prospective cross-sectional survey in four Danish university hospitals.

BACKGROUND: Pain management in hospitalized children is often inadequate. The prevalence and main sources of pain in Danish university hospitals is unknown. METHODS: This prospective mixed-method cross-sectional survey took place at four university hospitals in Denmark. We enrolled 570 pediatric patients who we asked to report their pain experience and its management during the previous 24 hours. For patients identified as having moderate to severe pain, patient characteristics and analgesia regimes were reviewed. RESULTS: Two hundred and thirteen children (37%) responded that they had experienced pain in the previous 24 hours. One hundred and thirty four (24%) indicated moderate to severe pain and 43% would have preferred an intervention to alleviate the pain. In children hospitalized for more than 24 hours, the prevalence of moderate/severe pain was significantly higher compared to children admitted the same day. The single most common painful procedure named by the children was needle procedures, such as blood draw and intravenous cannulation. CONCLUSION: This study reveals high pain prevalence in children across all age groups admitted to four Danish university hospitals. The majority of children in moderate to severe pain did not have a documented pain assessment, and evidence-based pharmacological and/or integrative ('non-pharmacological') measures were not systematically administered to prevent or treat pain. Thus, practice changes are needed.

Peripherally applied opioids for postoperative pain: evidence of an analgesic effect? A systematic review and meta-analysis.

BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity scores, consumption of supplemental analgesics and time to first analgesic were included. Trials with sample sizes of fewer than 10 patients per treatment group or trials with opioids administered intra-articularly or as peripheral nerve blocks were excluded. RESULTS: Data from 26 studies, including 1531 patients and 13 different surgical interventions were included. Clinical heterogeneity of the studies was substantial. Meta-analysis indicated statistically significant, but not clinically relevant, reductions in VAS score at 6-8 h (mean difference -4 mm, 95% CI: -6 to -2) and 12 h postoperatively (mean difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved postoperative analgesia. CONCLUSION: Evidence of a clinically relevant analgesic effect of peripherally applied opioids for acute postoperative pain is lacking. The analgesic effect of peripherally applied opioids may depend on the presence of preoperative inflammation.

A qualitative systematic review of peri-operative dextromethorphan in post-operative pain.

BACKGROUND: The N-methyl-D-aspartate (NMDA) receptor antagonist, dextromethorphan (DM), has received interest as an adjunctive agent in post-operative pain management. Clinical trials have been contradictory. This systematic review aims to evaluate the available literature examining the analgesic efficacy of DM in post-operative patients. METHODS: Twenty-eight randomized, double-blind, clinical studies, with 40 comparisons, including a variety of dosing regimens comparing DM treatment with placebo, were included. Meta-analysis was intended but deemed to be inappropriate because of the substantial difference in methodology and reporting between trials. The outcome measures (pain scores at rest, time to first analgesic request and supplemental analgesic consumption) were evaluated qualitatively by significant difference (P<0.05) as reported in the original investigations. RESULTS: DM did not reduce the post-operative pain score with a clinically significant magnitude. The time to first analgesic request was significantly prolonged in most comparisons with DM. Significant decreases in supplemental opioid consumption were observed in the majority of parenteral DM studies and in about one-half of the oral studies. The decreases were of questionable clinical importance in most comparisons, although a relationship between a decrease in opioid consumption and opioid-related side-effects was established in some studies. CONCLUSION: Based on the studies available, DM has the potential to be a safe adjunctive agent to opioid analgesia in post-operative pain management, but the consistency of the potential opioid-sparing and pain-reducing effect must be questioned. Consequently, it is not possible to recommend dose regimens or routine clinical use of DM in post-operative pain. The route of administration may be important for the beneficial effect.

Intra-operative remifentanil might influence pain levels in the immediate post-operative period after major abdominal surgery.

BACKGROUND: Remifentanil, a widely used analgesic agent in anaesthesia, has a rapid onset and short duration of action. In clinical settings, this requires an appropriate pain strategy to prevent unacceptable pain in the post-operative period. The aim of this study was to investigate whether remifentanil had any impact on post-operative pain and opioid consumption after major abdominal surgery. METHODS: Fifty patients undergoing major abdominal surgery were randomized to receive either remifentanil 0.4 microg/kg/min or placebo intra-operatively, in addition to basic combined general and epidural anaesthesia, in this double-blind study. Patients received patient-controlled analgesia with morphine for 24 h post-operatively. Morphine consumption, assessment of pain at rest and during coughing, side-effects and levels of sensory block were recorded during the first 24 h post-operatively. RESULTS: Twenty-one patients receiving remifentanil and 18 patients receiving placebo completed the study. The median visual analogue scale (VAS) score at rest from 0 to 2 h was significantly increased in the remifentanil group [40 mm (27-61 mm)] vs. placebo [13 mm (3-35 mm)] (P < 0.05). No significant differences in morphine consumption, VAS score during coughing or adverse effects were observed between the groups. CONCLUSION: The results are weak and difficult to interpret. They could indicate that a high dose of remifentanil added to otherwise sufficient combined general and epidural anaesthesia may induce opioid-induced hyperalgesia and/or clinically acute opioid tolerance after major abdominal surgery; however, as no significant differences could be observed between the groups after 2 h post-operatively, the clinical relevance of these observations is questionable.

Reduction of opioid-related adverse events using opioid-sparing analgesia with COX-2 inhibitors lacks documentation: a systematic review.

BACKGROUND: We have reviewed opioid-related adverse events in studies of opioid sparing with cyclooxygenase-2 (COX-2) inhibitors compared with placebo in postoperative pain. METHODS: Randomized, controlled trials were evaluated. Outcome measures were significant reduction in consumption of supplementary opioids with the COX-2 inhibitors and reported opioid-related adverse events (nausea, vomiting, constipation, dizziness, sedation, pruritus and/or urinary retention) 0-24 h after surgery. RESULTS: Nineteen studies including 26 comparisons of four COX-2 inhibitors (rofecoxib, celecoxib, parecoxib and valdecoxib) were evaluated, in which significant opioid-sparing averaging about 35% with COX-2 inhibitors and opioid-related adverse events were reported. The trials were in general of high quality (median Oxford quality score 4) but the reporting quality of adverse events was poor. Opioid-related adverse events, i.e. vomiting, constipation and pruritus, were only significantly reduced with COX-2 inhibitors in four of the 26 comparisons. Quantitative analysis of combined data revealed a significantly reduced risk for only dizziness; the clinical relevance was minor as the number needed to treat (NNT) was about 33. CONCLUSION: The limitation of this review is the lack of quality of data of adverse events from the original trials. Although supplementary opioid consumption in all trials was significantly reduced by on average 35% with the COX-2 inhibitors, it was only sporadically possible to demonstrate a clinically important reduction in opioid-related adverse events. Data did not support the common opinion that opioid-sparing with COX-2 inhibitors provides much clinical beneficial effect with respect to opioid-related adverse events. Future studies have to increase the awareness and proper reporting of adverse events in the postoperative period.

A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain.

BACKGROUND: We have reviewed the analgesic efficacy of cyclooxygenase-2 (COX-2) inhibitors compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs), different COX-2 inhibitors, and placebo in post-operative pain. METHODS: Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia 0-24 h after surgery. RESULTS: Thirty-three studies were included in which four COX-2 inhibitors, rofecoxib 50 mg, celecoxib 200 and 400 mg, parecoxib 20, 40 and 80 mg, and valdecoxib 10, 20, 40, 80 mg were evaluated. Ten of these studies included 18 comparisons of rofecoxib, celecoxib, or parecoxib with NSAIDs. Rofecoxib 50 mg and parecoxib 40 mg provided analgesic efficacy comparable to that of the NSAIDs in the comparisons, and with a longer duration of action after dental surgery but possibly not after major procedures. Celecoxib 200 mg and parecoxib 20 mg provided less effective pain relief. Four studies included five comparisons of rofecoxib 50 mg with celecoxib 200 and 400 mg. Rofecoxib 50 mg provided superior analgesic effect compared with celecoxib 200 mg. Data on celecoxib 400 mg were too sparse for firm conclusions. Thirty-three studies included 62 comparisons of the four COX-2 inhibitors with placebo and the COX-2 inhibitors significantly decreased post-operative pain. CONCLUSION: Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in post-operative pain after minor and major surgical procedures, and after dental surgery these COX-2 inhibitors have a longer duration of action. Besides, rofecoxib 50 mg provides superior analgesic effect compared with celecoxib 200 mg.

Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial.

BACKGROUND: Preliminary clinical studies have suggested that gabapentin may produce analgesia and reduce the need for opioids in postoperative patients. The aim of the present study was to investigate the opioid-sparing and analgesic effects of gabapentin administered during the first 24 h after abdominal hysterectomy. METHODS: In a randomized, double-blind study, 80 patients received oral gabapentin 1200 mg or placebo 1 h before surgery, followed by oral gabapentin 600 mg or placebo 8, 16 and 24 h after the initial dose. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 24 h postoperatively. Pain was assessed on a visual analogue scale (VAS) at rest and during mobilization, nausea, somnolence and dizziness on a four-point verbal scale, and vomiting as present/not present at 2, 4, 22 and 24 h postoperatively. RESULTS: Thirty-nine patients in the gabapentin group, and 32 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from median 63 (interquartile range 53-88) mg to 43 (28-60) mg (P < 0.001). We observed a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0 to 2 h, and from 0 to 4 h postoperatively (R2 = 0.30, P = 0.003 and R2 = 0.24 P = 0.008, respectively). No significant differences in pain at rest or during mobilization, or in side-effects, were observed between groups. CONCLUSION: Gabapentin in a total dose of 3000 mg, administered before and during the first 24 h after abdominal hysterectomy, reduced morphine consumption with 32%, without significant effects on pain scores. No significant differences in side-effects were observed between study-groups.

Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia.

BACKGROUND: We have reviewed the analgesic efficacies of rectal and parenteral paracetamol and tested the evidence for a possible additive analgesic effect of the combination of paracetamol with a non-steroidal anti-inflammatory drug (NSAID) in postoperative pain. METHODS: Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia. RESULTS: Eight studies compared rectal paracetamol with placebo. One study of single-dose administration of rectal paracetamol 40-60 mg kg(-1) and three studies of repeat dosing with 14-20 mg kg(-1) showed significant analgesic efficacy, while studies of a single dose of 10-20 mg kg(-1) were negative. Ten studies compared parenteral paracetamol with placebo and eight studies showed improved pain relief with paracetamol. Of the nine studies comparing paracetamol with a combination of paracetamol and an NSAID, six studies showed improved pain relief for the combination while only two of the six studies comparing an NSAID with a combination of an NSAID and paracetamol showed improved pain relief for the combination. CONCLUSIONS: Considering the few studies available, evidence was found of a clinically relevant analgesic effect of rectal and parenteral paracetamol. Concurrent use of paracetamol and an NSAID was superior to paracetamol alone but no evidence was found of superior analgesic effect of the combination compared with the NSAID alone.

Postoperative analgesia is not different after local vs systemic administration of meloxicam in patients undergoing inguinal hernia repair.

PURPOSE: To distinguish between local and systemic drug effects, we compared pain scores, analgesic consumption and plasma concentrations after local vs i.v. administration of meloxicam 7.5 mg in patients with inguinal hernia repair. METHODS: In a double-blind, randomized study 56 patients received either local or i.v. meloxicam 7.5 mg. Postoperative pain was assessed with a visual analogue scale (VAS) at rest, on mobilization, and on coughing, the need for supplementary analgesics (fentanyl i.v. and/or acetaminophen-codeine tablets) was recorded, and blood samples were drawn during 24 hr after meloxicam administration. RESULTS: No significant differences were found between groups with respect to pain scores, or in the consumption of supplementary analgesics. Following local application of meloxicam, the peak plasma concentration (C(max)) of 0.5 +/- 0.2 mg*L(-1) achieved after 1.8 +/- 0.5 hr was much lower than the C(max) of 2.5 +/- 0.9 mg*L(-1) achieved immediately after i.v. administration (P <0.05). Mean meloxicam plasma concentration after infiltration was significantly lower than after i.v. doses for the first three hours after administration (P <0.05). CONCLUSION: We showed no differences in pain scores and analgesic consumption between local and i.v. administration of meloxicam 7.5 mg during the first 24 hr after herniorrhaphy, while plasma concentration of meloxicam was lower after local administration. These results indicate a lack of difference in pain relief after concentrating meloxicam at the hernia wound or after achieving high blood levels rapidly (i.v.). Local administration of meloxicam may confer an advantage over systemic administration by eliciting lower incidences of systemic adverse effects.

Pharmacokinetics of oral diclofenac and acetaminophen in children after surgery.

BACKGROUND: Our aim was to study the pharmacokinetics and pain scores following administration of single oral doses of either diclofenac or high-dose acetaminophen (paracetamol). METHODS: In the morning, the day after tonsillectomy, children 5-15 years of age were randomized in a double-blind manner to receive either diclofenac 1-2 mg.kg-1 (n=11) or acetaminophen 22.5 mg.kg-1 (n=10). Postoperative pain was assessed by self-report and blood samples were drawn every 30 min for 4 h after medication. RESULTS: Large interindividual differences in maximum plasma diclofenac concentrations (Cmax) were found. Mean Cmax was 2.4+/-1.3 microg.ml-1 and mean tmax was 2+/-0.5 h. No significant reduction in pain score with diclofenac was seen at any of the assessments during the study period. Eight of 10 children achieved Cmax of acetaminophen within the 10-20 microg.ml-1 antipyretic range. Mean tabs was 0.7+/-0.3 h and mean Cmax and tmax were 12.7+/-3.8 microg ml-1 and 1.4+/-0.5 h, respectively. No significant reduction in pain score with acetaminophen was seen at any of the assessments during the study period. CONCLUSIONS: The achieved concentrations of diclofenac and acetaminophen were not able to significantly reduce the children's pain score during the 5 h postingestion study period. Analgesic plasma acetaminophen concentrations may be higher than those required for antipyresis.

Local infiltration with NSAIDs for postoperative analgesia: evidence for a peripheral analgesic action.

BACKGROUND: In order to investigate the evidence for a peripheral analgesic effect of local infiltration with nonsteroidal antiinflammatory drugs (NSAIDs) in postoperative pain, we conducted a systematic review. METHODS: Randomised controlled and double-blind trials were evaluated. Outcome measures were pain scores, the use of supplementary analgesics, and time to first analgesic request. Efficacy was estimated by significant difference (P<0.05) as reported in the original reports and by calculation of the weighted mean difference of pain scores between treatment groups. RESULTS: Sixteen studies with data from 844 patients were considered appropriate for analysis. The NSAIDs were administered as intra-articular injections, as components of intravenous regional anaesthesia (IVRA), and by wound infiltration and were compared with systemic administration or placebo. In the four studies comparing intra-articular NSAIDs with systemic administration a statistically significant effect in favour of intraarticular NSAIDs was found. Only one study compared IVRA NSAID with systemic administration, showing a significant effect in favour of IVRA administration. No more than two of the five studies comparing intrawound NSAIDs with systemic administration showed significant effect after intrawound administration. Most of the studies comparing local infiltration with placebo showed significant effect in favour of local infiltration. CONCLUSION: There is evidence for a clinically relevant peripheral analgesic action of intra-articular NSAIDs while results of IVRA and wound infiltration with NSAIDs in postoperative pain are inconclusive. Trials without a systemic control group were not considered to provide evidence for a local effect.

Diclofenac or acetaminophen for analgesia in paediatric tonsillectomy outpatients.

BACKGROUND: In order to establish an effective drug regimen, we compared the analgesic efficacy of oral diclofenac and high-dose acetaminophen on pain after tonsillectomy. METHODS: In this randomised, double-blind study 48 children, 5 to 15 years of age, following tonsillectomy were assigned to receive either diclofenac 2-3 mg kg(-1) 24 h(-1) (n=24) or acetaminophen 90 mg kg(-1) 24 h(-1) (n=24) for the first three days after surgery. Postoperative pain was assessed by self-report each day before scheduled medication at 7 h, 12 h, 18 h and 23 h. RESULTS: The number of children rating severe pain was high in both the diclofenac group, 5-50%, and in the acetaminophen group, 12-58% during the three day study period. Pain scores in the diclofenac group were only significantly lower at 12 h on day 1-3 compared to pain scores in the acetaminophen group (P<0.05). None of the children in the diclofenac group experienced any episodes of nausea/vomiting compared to 9 children in the acetaminophen group on day 1. The incidences of nausea/vomiting increased with pain (P<0.05). None of the 48 children experienced any episodes of bleeding. CONCLUSIONS: This study indicates that diclofenac was no more effective than high-dose acetaminophen (90 mg vs. 60 mg kg(-1) 24 h(-1)) for analgesia, but resulted in a lower incidence of nausea and vomiting in patients following tonsillectomy.

Tetracaine gel vs EMLA cream for percutaneous anaesthesia in children.

We have evaluated the anaesthetic effect of tetracaine gel 1 g, applied for 45 min, compared with EMLA cream 2 g, applied for 60 min, in a randomized, double-blind study in 60 children aged 3-15 yr. Venous cannulation was performed 15 min after removal of the EMLA cream (n = 20) and tetracaine gel (n = 20). Cannulation was performed up to 215 min after removal of the tetracaine gel in another 20 patients. Significantly lower pain scores were recorded by the children treated with tetracaine gel compared with EMLA cream (P < 0.02). Forty to 45% of children in the tetracaine groups reported no pain compared with only 10% in the EMLA group. Only minor adverse effects were observed. We conclude that tetracaine gel provided effective, rapid, long-lasting and safe local anaesthesia, and was significantly better than EMLA cream in reducing pain during venous cannulation in children using the recommended application periods for both formulations.

Analgesic efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy.

BACKGROUND: Tonsillectomy is a common procedure in childhood resulting in significant morbidity due to pain. The aim of this study was to evaluate the analgesic efficacy and safety of a single dose of ketorolac i.v. given before or after tonsillectomy, compared to placebo. METHODS: A randomized, double-blind, placebo-controlled study was performed in 60 children, 5 to 15 years of age, admitted for tonsillectomy. Patients were allocated to receive ketorolac 1 mg.kg-1 i.v. or placebo. Postoperative pain was assessed by self-report 1.5, 3, 5, and 24 h after surgery. RESULTS: Pain scores were significantly lower for both ketorolac groups compared to the placebo group 1.5, 3, and 5 h after surgery (P = 0.05). Pain scores were lowest in the preoperative ketorolac group 1.5 to 5 h after surgery, and significantly fewer children in this group had fentanyl 0 to 1.5 hr after surgery. But no significant differences were found between pain scores of the preoperative and postoperative ketorolac groups in the first 24 h after surgery. Acetaminophen consumption during the first 5 h after surgery was significantly less in patients receiving ketorolac (P < 0.05). Patients in the preoperative ketorolac group had a significantly lower incidence of postoperative vomiting (P < 0.05). There were no significant differences in the incidence of postoperative bleeding between groups. Three children in the preoperative, 5 children in the postoperative ketorolac group and 5 children in the placebo group experienced postoperative haemorrhage. CONCLUSION: This study indicates that a single dose of ketorolac 1 mg.kg-1 i.v. administered either before or immediately after surgery improves postoperative analgesia in children after tonsillectomy without evidence of increased incidence of bleeding.

Examination of acetaminophen for outpatient management of postoperative pain in children.

We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy.

Peri-operative use of nonsteroidal anti-inflammatory drugs in children: analgesic efficacy and bleeding.

Nonsteroidal anti-inflammatory drugs are effective in the management of mild to moderate postoperative pain in children. They can decrease or even eliminate the need for opioid analgesics, thus reducing or eliminating opioid-induced side-effects. The increasing peri-operative use of nonsteroidal anti-inflammatory drugs in children has, however, raised concerns about complications secondary to impaired haemostasis. To examine the extent of this unwanted side-effect, this paper reviews the published literature on analgesic efficacy and bleeding following the peri-operative use of nonsteroidal anti-inflammatory drugs in children. The reviewed literature confirms that haemorrhagic events in the postoperative period occur, but results remain inconclusive regarding the association between peri-operative use of nonsteroidal anti-inflammatory drugs and disordered haemostasis. In order to maximise the benefit of nonsteroidal anti-inflammatory drugs in children, the risks must be recognised and patients, clinical indications, the individual drug, timing and route of administration must be selected carefully. Nonsteroidal anti-inflammatory drugs appear to play a valuable role in the further improvement of postoperative pain management in children.

[Parents' expectations and evaluation of their children's postoperative pain treatment]. / Foraeldres forventning til og vurdering af deres børns postoperative smertebehandling.

In order to improve postoperative pain management in children, the parents of 31 elective surgical children, three months to 15 years of age, were asked preoperatively about their expectations regarding their children's postoperative pain and pain relief. At 24 hours after surgery, the parents were asked about their perceptions of their children's pain and pain control. The survey indicates that the parents had high expectations of good pain relief. Eighty percent wanted effective analgesia administered promptly when the children had some pain. On the whole the parents' perceptions corresponded to their expectations. However, current practice in controlling pain after surgery is still not optimal. Twenty-nine percent (9) of the children experienced severe or unbearable pain or experienced pain for all of the 24 h after surgery. An approach to improve pain management in children could be for the hospital staff to reorganize and to develop an "acute pain service". A pain service may not require new technology, but could instead be based on more effective communication and skill in utilizing the traditional systems.

[Postoperative pain in children. A comparison between ratings of children and nurses]. / Postoperative smerter hos børn. Sammenligning mellem børnenes og sygeplejerskernes vurderinger.

Several predominantly North American studies indicate that postoperative pain experienced by children is underestimated by the nurses, who are in charge of the analgesic treatment of the children's pain. The purpose of this investigation was to examine, in Danish children, the relationship between the children's ratings of their pain and the nurses' ratings of the children's pain. The issue was examined by comparing the pain ratings of 100 children three to 15 years of age following tonsillectomy. The ratings were obtained by using the Poker Chip Tool and a 10-cm Visual analogue scale. The differences between the children's and the nurses' pain ratings were most pronounced after administration of analgesics (p < 0.001). After analgesics, the children's mean pain score was 17% lower than before analgesics, while the nurses' mean pain scores of the children's pain were 53-58% lower than before analgesics. Consistent with results from foreign studies, this Danish study found that, in general, the nurses underestimated the children's pain. The nurses tended to overestimate the effect of analgesics and tended to modify their pain ratings according to the children's level of activity.

Pain assessment of subcutaneous injections.

OBJECTIVE: To compare injection pain after subcutaneous administration of four different solution volumes. DESIGN: Double-blind, randomized, prospective, multiple crossover study. SETTING: Steno Diabetes Center, Gentofte, Denmark. PARTICIPANTS: Eighteen healthy volunteers, 9 women and 9 men, aged 21-30 years. METHODS: The subjects were injected with four different volumes (0.2, 0.5, 1.0, 1.5 mL) of NaCl 0.9%. The study was performed on 2 days with a 1-week washout period between the study days. On each study day the subjects received four injections in each thigh. To evaluate the validity of our pain assessing model the subjects received eight injections of 0.5% mL on one of the study days. Pain assessment was done immediately after each injection using both a 10-cm visual analog scale (VAS) and a six-item verbal rating scale (VRS). RESULTS: A significant difference in pain score on both the VAS (p < 0.05) and the VRS (p < 0.01) was seen between the four injection volumes. The pain was significantly increased with volumes of 1.0 and 1.5 mL. No significant difference in injection pain could be detected between 0.2 and 0.5 mL and between 1.0 and 1.5 mL. No significant period or carryover effect could be detected in the study. A significant correlation between the pain score on the VAS and the pain score on the VRS was found (r = 0.79, p < 0.0001). CONCLUSIONS: The pain of a subcutaneous injection is related to injection volume in the thigh. The results show that increasing the volume from 0.5 to 1.0 mL increases the pain significantly. The findings from this study should be considered when injection preparations for subcutaneous administration are formulated. The volume should generally be less than 1.0 mL if injected into the thigh.