Chronic morphine increases Fos-positive neurons after concurrent cornea and tail stimulation

Objective.— The aim of the present study was to examine the effect of chronic morphine exposure on diffuse noxious inhibitory controls in a large population of neurons throughout the medullary dorsal horn, as assessed using immunocytochemistry for c‐Fos protein. Background.— Overuse of medications, including the opioids, to treat migraine headache can lead to progressively more frequent headaches. In addition, chronic daily headache sufferers and chronic opioid users both lack the inhibition of pain produced by noxious stimulation of a distal body region, often referred to as diffuse noxious inhibitory controls. Methods.— In urethane anesthetized rats, Fos‐positive neurons were quantified in chronic morphine and vehicle‐treated animals following 52°C noxious thermal stimulation of the cornea with and without the application of a spatially remote noxious stimulus (placement of the tail in 55°C water). Results.— When compared to chronic morphine‐treated animals that did not receive the spatially remote noxious stimulus, chronic morphine‐treated animals given corneal stimulation along with the spatially remote noxious stimulus demonstrated a 163% increase (P < .05) in the number of Fos‐positive neurons in the superficial laminae of the medullary dorsal horn and a 682% increase (P < .01) in deep laminae that was restricted to the side ipsilateral to the applied stimulus. In contrast, no significant difference was found in Fos‐like immunoreactivity in vehicle‐treated animals given concurrent cornea and tail stimulation or only cornea stimulation in either superficial or deep laminae. Conclusions.— It is proposed that an increase in descending facilitation and subsequent loss of diffuse noxious inhibitory controls contributes to the development of medication overuse headache.     

硬膜外吗啡－氟哌啶术后镇痛效果及并发症影响因素观察

目的 :探讨硬膜外吗啡—氟哌啶术后镇痛效果及并发症影响因素。方法 :57例硬膜外阻滞下施术病人 ,于手术结束时经硬膜外腔导管注入吗啡—氟哌啶混合液。术后随访72h ,观察不现年龄、性别、术式、给药部位对24h镇痛率(镇痛时间>24h)、48h肠蠕动恢复率(48h内排气)和恶心呕吐发生率的影响。结果 :随年龄增长24h镇痛率增高(P<0.01) ,48h肠蠕动恢复率低(P<0.05) ;女性呕吐发生率高于男性(P<0.05) ;腹部手术48h肠蠕动恢复率低于非腹部手术 ;中低位硬外组48h肠蠕动恢复率低于高位硬外组。结论 :年龄影响吗啡—氟哌啶术后镇痛效果 ;年龄、术式、给药部位影响肠蠕动恢复 ;性别影响恶心呕吐发生率。     

Differential effects of morphine on the affective and the sensory component of carrageenan-induced nociception in the rat

Pain is generally considered to have a sensory and an affective component. Clinical research has suggested that morphine more potently attenuates the affective component as compared to the sensory component. Because preclinical nociception models typically focus on the sensory component of nociception, and do not assess the affective component, it is unclear whether this potency difference of morphine can also be found in preclinical models. We therefore adapted the place conditioning paradigm to investigate negative affect accompanying carrageenan-induced (0.5% intraplantar) inflammatory nociception in rats. We found that carrageenan produced clear conditioned place aversion (CPA). Morphine (0.01-10mg/kg i.p.) dose-dependently reduced carrageenan-induced CPA with a minimal effective dose (MED) of 0.03mg/kg. Since morphine has a rewarding effect by itself, morphine-induced conditioned place preference (CPP) was also investigated. Morphine induced CPP with a MED of 1mg/kg, suggesting that the rewarding effect of morphine was not responsible for reducing carrageenan-induced CPA. We also demonstrated that morphine reduced carrageenan-induced mechanical nociception as assessed in the Randall Selitto paradigm with a MED of 1mg/kg. It is concluded that the CPA model allows for an assessment of the negative affective component of carrageenan-induced nociception. Moreover, morphine was able to reduce the affective component of nociception at doses that did not affect the sensory component of nociception, and this effect was not due to its rewarding properties. The fact that this finding mirrors the clinical situation validates the use of the CPA model for assessing the affective component of nociception.     

A retrospective study on the use of oral morphine in cancer pain

The authors report a retrospective study of 390 cancer pain patients tested with oral morphine during a four-month period. Initial pain scores were reduced to one half after one week of treatment and then maintained throughout the study period. Mean daily dosages of morphine were lower in those patients 65 years and older. No significant changes in performance in relation to therapy were noted except for an increase in hours of sleep. An accurate titration of dosage and continued control of side effects are the main requirements of this method of administration. The presence of side effects and the cause of interruption of treatment are reported.     

Epidural ketamine potentiates epidural morphine but not fentanyl in acute nociception in rats.

Epidural opioids have been reported to provide superior analgesia in acute pain management. Despite the fact that the required doses are low, major side effects such as respiratory depression may still occur. In an effort to maximize analgesia and to minimize the rate of side effects, epidural NMDA receptor antagonists, especially ketamine, may be co-administered with opioids. This study investigated whether ketamine had beneficial effects on fentanyl- or morphine-induced antinociception in an acute pain model in rats.In male Wistar rats, an epidural catheter was placed under general anaesthesia. After 1 week the animals were subjected to the tail withdrawal reaction (TWR) test. After determination of the basal reaction latencies, fentanyl, morphine, ketamine or combinations of an opioid with ketamine were administered epidurally. TWR latencies were measured for up to 2h after treatment.Both opioids showed a dose related antinociceptive effect. Fentanyl had a fast onset and a short duration of action whereas the reverse was true for morphine. Ketamine exhibited only limited antinociceptive properties. In the combinations, ketamine improved morphine-induced antinociception both in terms of maximal possible effect (MPE) as well as in duration of action. The combination of fentanyl with ketamine did not result in any improvement, neither in terms of MPE nor in duration of action. Moreover, increasing doses of ketamine tended to decrease the MPE of various doses of fentanyl. These data confirm that ketamine, contrary to opioids, does not possess important antinociceptive properties in an acute test such as the TWR test. Furthermore, these data indicate that additive drugs such as ketamine may have different effects on different opioids.     

Systemic physostigmine increases the antinociceptive effect of spinal morphine

In this study we evaluated the antinociceptive effect of concurrent intrathecal (i.t.) and subcutaneous (s.c.) administration of morphine and physostigmine, respectively. The experiments were performed on male Wistar rats. Intrathecal administration of morphine was performed through a catheter implanted in the subarachnoid space. The ‘tail-immersion' test was used to measure animals' responses to evoked nociceptive stimuli. Interaction of drugs was analyzed using a dose addition model. Both i.t. (1–5 μg) administration of morphine and s.c. (50–250 μg/kg) administration of physostigmine increased the latencies of nociceptive responses in a dose-dependent manner. Two micrograms of i.t. morphine and 100 μg/kg of s.c. physostigmine demonstrated 31.6±10.6 and 34.2±11.4 percentage of maximal possible effect (%MPE), respectively. Simultaneous administration of 1 μg of i.t. morphine and 50 μg/kg of s.c. physostigmine produced a %MPE equal to 84.8±16.9. Thus, combined administration of 1 μg i.t. morphine and 50 μg/kg s.c. physostigmine resulted in a strong, highly significant antinociceptive effect. This effect was much higher than the effect expected if both drugs acted in an additive manner. Supra-additive interaction observed in this study might be a result of simultaneous activation of different neurotransmitter systems involved in nociceptive processing at the spinal as well as at the supraspinal level of the CNS.     

Hypoxaemia after lower abdominal surgery: Comparison of tramadol and morphine

This prospective, double-blind, randomised study measured postoperative arterial oxygen saturation (SpO₂) in 27 female patients (aged 28–68 years; ASA I–III) allocated to receive parenteral tramadol or morphine in equianalgesic doses following an abdominal (Pfannenstiel) incision. Benzodiazepine premedication was followed by a standardised general anaesthetic, including fentanyl intra-operatively. The first dose of study analgesic medication was administered postoperatively more than one hour after the last increment of fentanyl. Pain was measured during the first eight hours using a four-point verbal rating scale. An overall opinion of the analgesia (using a five-point verbal rating scale) was noted at 24 hours post surgery. SpO₂ while breathing air was recorded every 30 seconds up to 24 hours postoperatively.Patient characteristics, pain scores and overall patient satisfaction were similar. Patients in the tramadol group spent significantly more time with normal saturation (SpO₂ > 94%, p=0.035): five of 12 patients in the morphine group were mildly hypoxaemic for more than 50% of study time (SpO₂ 90–94%) compared to only two of the 13 patients in the tramadol group. The incidence of moderate hypoxaemia (SpO₂ 85–89%) was higher in the morphine group. Severe hypoxaemia (SpO₂ < 85%) was infrequent in both groups, but of greater incidence in the morphine group. Tramadol produced a significantly lower incidence of arterial hypoxaemia than morphine.     

Melatonin and morphine: potential beneficial effects of co‐use

Morphine is a potent analgesic agent used to control acute or chronic pain. Chronic administration of morphine results in analgesic tolerance, hyperalgesia, and other side effects including dependence, addiction, respiratory depression, and constipation, which limit its clinical usage. Therefore, identifying the new analgesics with fewer side effects which could increase the effect of morphine and reduce its side effects is crucial. Melatonin, a multifunctional molecule produced in the body, is known to play an important role in pain regulation. The strong anti‐inflammatory effect of melatonin is suggested to be involved in the attenuation of the pain associated with inflammation. Melatonin also increases the anti‐nociceptive actions of opioids, such as morphine, and reverses their tolerance through regulating several cellular signaling pathways. In this review, published articles evaluating the effect of the co‐consumption of melatonin and morphine in different conditions were investigated. Our results show that melatonin has pain‐killing properties when administered alone or in combination with other anti‐nociceptive drugs. Melatonin decreases morphine consumption in different pathologies. Furthermore, attenuation of morphine intake can be accompanied by reduction of morphine‐associated side‐effects, including physical dependence, morphine tolerance, and morphine‐related hyperalgesia. Therefore, it is reasonable to believe that the combination of melatonin with morphine could reduce morphine‐induced tolerance and hyperalgesia, which may result from anti‐inflammatory and antioxidant properties of melatonin. Overall, we underscore that, to further ameliorate patients' life quality and control their pain in various pathological conditions, melatonin deserves to be used with morphine by anesthesiologists in clinical practice.     

The influence of hemorrhagic shock on the pharmacokinetics and the analgesic effect of morphine in the rat

Summary— The influence of hemorrhagic shock (removal of 30% of the blood volume) on the pharmacokinetics and the analgesic effect of morphine was investigated in conscious rats. Plasma concentrations of morphine after a bolus injection (5 mg/kg) are higher in the shock animals, which is attributed to a small decrease in clearance (-22%; P > 0.05) and a significant decrease in distribution volume (-33%; P < 0.05) of the drug. The areas under the plasma concentration-time curve of the metabolite morphine-3-glucuronide (M3G) are significantly higher (+237%; P < 0.01) in the shock rats, which is probably explained by a decreased distribution and renal excretion. The analgesic effect of morphine was evaluated using the tail-flick test during a continuous infusion (10 mg/kg/h) with measurement of the plasma concentrations of morphine and M3G. Data from these experiments show higher plasma concentrations of morphine (+33%; P < 0.05) and M3G (+66%; P > 0.05) during shock, and a significantly increased analgesic effect (+43%; P < 0.05). Our data suggest that the increased analgesic effect of morphine during hemorrhagic shock can most likely be explained by pharmacokinetic changes resulting in higher morphine concentrations.     

Efficacy and safety of tramadol and morphine in patients with extremely severe postoperative pain

Tramadol is used for postoperative pain management. However, it is unknown whether tramadol has the same analgesic efficacy as morphine in patients with extremely severe pain. Respiratory depression and sedation by the applied drugs is of special interest.This prospective, randomised, double-blind study was performed as a pilot study. After standardised general anaesthesia, 20 patients with extremely severe postoperative pain — visual analogue scale ≥8 (VAS) — were allocated to intravenous pain treatment with either tramadol or morphine. The goal was to reduce pain intensity to VAS ≤1 during a four hour period. Pain intensities, vital parameters and side effects were recorded every 15 minutes. Sedation (four-point scale) and blood gases were controlled every 30 minutes. Oxygen saturation was continuously monitored by pulse oximetry. An oxygen saturation below 90% without oxygen supply was taken as respiratory depression. Statistical analysis was performed with the t-test for most of the numerical parameters. A p-value <0.05 was considered significant.Both drugs reduced pain intensities to VAS ≤1 within 135 minutes (median). Median dosages were 292.5 mg for tramadol (160–460 mg) and 27 mg for morphine (20–45.1 mg). Tramadol patients experienced significantly fewer severe side effects: two morphine patients had to be excluded from the efficacy analysis of the study: one for extreme sedation, the other because of severe respiratory depression. Minor side effects had a similar incidence.In conclusion, successful treatment of extremely severe postoperative pain was achieved with both tramadol and morphine. Drug dosages were significantly higher than usually administered. Tramadol patients experienced fewer severe side effects than morphine patients.     

Morphine responsiveness in a group of well-defined multiple sclerosis patients: a study with i.v. morphine.

Pain in multiple sclerosis (MS) is more common than has previously been believed. About 28% of all MS patients suffer from central pain (CP), a pain that is difficult to treat. In the present study we have investigated the responsiveness of this pain to morphine. Fourteen opioid-free patients (eight woman and six men) with constant, non-fluctuating, long-lasting CP caused by MS were investigated. Placebo (normal saline), morphine and naloxone were given intravenously in a standardized manner. The study design was non-randomized, single blind and placebo controlled. Ten patients experienced less than 50% pain reduction by placebo and less than 50% pain reduction by morphine. Four patients were opioid responders, i.e. had minimal or no effect on pain by placebo, >50% pain reduction after morphine and >25% pain increase after naloxone, given intravenously following morphine. However, this response was obtained after high doses of morphine (43 mg, 47 mg, 50 mg and 25 mg; mean 41 mg). Thus, compared with nociceptive pain, only a minority of the patients with CP due to MS responded to morphine and only at high doses. The present results are in accord with experimental studies indicating that neuropathic pain is poorly responsive but not totally unresponsive to opioids. The results do not support the routine use of strong opioids in MS patients with CP.     

Differential effects of morphine on pain and temperature perception in human volunteers

Electrophysiological and behavioral evidence suggests that morphine may have a differential effect on nociceptive and thermal pathways. In this study, we explored the perceptual consequences of these differential actions by examining the effect of a low morphine dose (0.08 mg/kg) on pain and temperature sensations arising from cutaneous thermal stimuli. In a double-blind placebo-controled study, we compared the perceived temperature intensity and perceived pain intensity and unpleasantness of noxious and innocuous heat and cold applied to the face of human subjects, with and without low doses of systemic morphine. The results showed that morphine modified pain-related sensations. In contrast, perceived thermal intensity of both noxious and innocuous heat or cold stimuli was unchanged by low-dose morphine administration. These findings suggest that low doses of morphine have a differential effect on pain and temperature sensations arising from the same stimulus, and thus that these sensations could be subserved by different neuronal populations.     

Age-related changes in vascular sympathetic neurotransmission in the rat kidney.

The objective of this study was to determine the effects of aging on sympathetic neurotransmission in an important vascular resistance bed, the kidney. The experimental model utilized was the isolated perfused kidney from male Fischer 344 rats, 6, 12 and 24 months of age. Stimulus-induced (supramaximal V, 30 pulses, 1 msec) overflow of endogenous norepinephrine was examined over a wide range of frequencies (0.25-12 Hz) under three conditions: 1) control; 2) after inhibition of neuronal and extraneuronal uptake; and 3) after blockade of alpha adrenoceptors. Absolute overflow of norepinephrine was significantly greater in the 24-month group compared to the 6- and 12-month groups. Because renal catecholamine content was not significantly different between the three groups, fractional overflow also was significantly greater in the 24-month group. Despite the increase in overflow in the 24-month group, control vasoconstrictor responses to nerve stimulation were not significantly different between the three groups. Inhibition of neuronal and extraneuronal uptake did not significantly alter the relationship between fractional overflows in the three groups. In the presence of alpha adrenoceptor blockade, utilized to eliminate the influence of inhibitory prejunctional alpha adrenoceptors, fractional overflow of norepinephrine was increased in each group compared to control. However, after alpha adrenoceptor blockade, fractional overflow was not significantly different between the three age groups. In conclusion, aging results in a decrease in prejunctional alpha adrenoceptor influence and increase in norepinephrine release from renal sympathetic nerves, but not alterations in vascular response to sympathetic nerve activation.     

Involvement of N-methyl-D-aspartate receptors in nociception in the cyclophosphamide-induced vesical pain model in the conscious rat.

We previously showed that the intraperitoneal (i.p.) administration of 200mg/kg cyclophosphamide, an antitumoral agent, modified the behaviour of rats with cystitis induced by acrolein, a toxic urinary by-product of cyclophosphamide. This behaviour, (namely decreased breathing rate, closing of the eyes, and specific postures), was scored to indirectly assess the nociception elicited by the cystitis and to use this experimental model as a vesical pain model. Here we investigated the involvement of the N-methyl-D-aspartate (NMDA) receptors and thus of the excitatory amino acid system in this model.We administered dizocilpine (0.01 to 0.1mg/kg intravenously (i.v.) and 1 to 20 microg/rat intrathecally (i.t.)) and ketamine (5 and 10mg/kg i.v. and 50 to 1000 microg/rat i.t.), two non-competitive NMDA receptor antagonists that bind to the channel site, and AP-5 (0.01 to 1mg/kg i.v. and 20 to 500 microg/rat i.t), a competitive antagonist that binds to the glutamate site. Whichever the route of administration (i.v. or i.t.), dizocilpine dose-relatedly reduced the behavioural disorders induced by cyclophosphamide. Systemic ketamine also dose-dependently, though transiently, reduced the effects of cyclophosphamide, but ketamine i.t. and AP-5 i.v. and i.t. did not induce any reduction of these effects.These results (i) demonstrate that in the cyclophosphamide-induced vesical pain model NMDA receptors are involved in the nociception, as shown by the effects of dizocilpine and systemic ketamine, (ii) reveal marked differences in the data obtained with various NMDA receptor antagonists, possibly due to their physicochemical properties, to the animal pain model used, to the noxious stimulus applied or to any combination of these factors.     

Effect of preoperative oral sustained-release morphine sulfate on postoperative morphine requirements in elective spine surgery

Sustained-release morphine sulfate (SRMS) is a painkiller used in oncology. The purpose of our study was to assess its efficacy on postoperative morphine requirements in elective spine surgery. This was a placebo-controlled, randomized, double-blind study. Adults scheduled for spine surgery under general anesthesia were orally administered SRMS (30 mg) or a placebo 2 h before surgery. Primary endpoint was postoperative cumulated morphine consumption through patient-controlled analgesia (PCA) during the 12 h following extubation. Statistical analysis was performed using a sequential method, the triangular test. The study was stopped after the sixth analysis (51 patients had been included; placebo: 26, SRMS: 25). Age, weight, sex ratio, type of surgery, intra-operative sufentanil consumption, anesthesia duration and time to extubation were similar in the two groups. Morphine consumption through PCA during the 12 h following extubation was significantly lower in the SRMS group (mean +/- SD: 10.5 +/- 7.6 mg) compared with placebo group (15.6 +/- 6.0 mg, P = 0.016, sequential analysis). Corresponding unbiased median estimates were 10.6 and 15.8 mg in SRMS and placebo groups, respectively. Morphine consumption through PCA during the 24 h following extubation was also significantly lower in the SRMS group (15.9 +/- 12.7 mg) compared with the placebo group (23.8 +/- 10.9 mg, P = 0.032). Vigilance, nausea and respiratory rate 3 and 6 h after extubation were similar in the two groups. A preoperative oral administration of SRMS (30 mg) induces a 33% reduction of postoperative morphine requirements in patients scheduled for spine surgery without inducing side effects.     

Effectiveness of polymer-coated extended-release morphine sulfate capsules in older patients with persistent moderate-to-severe pain: A subgroup analysis of a large, open-label, community-based trial

Abstract

Background:

Opioid analgesics may offer benefits over nonopioids in some older patients, especially those with moderate-to-severe pain. Polymer-coated extended-release morphine sulfate (P-ERMS) has been found to be efficacious and well tolerated in patients with chronic, moderate-to-severe, nonmalignant pain when used QD or BID.

Objective:

The purpose of this analysis was to determine the effectiveness of P-ERMS in older patients (aged >65 years) with persistent, moderate-to-severe, inadequately controlled, nonmalignant pain.

Methods:

This was a subgroup analysis of the older population from an openlabel trial in community-based pain clinics in which patients underwent treatment with P-ERMS for persistent, moderate-to-severe, inadequately controlled, nonmalignant pain (≥4 on a scale of 0–10). Patients received P-ERMS at a dose determined by the investigator based on their previous analgesic regimen, QD (morning or evening) for a 4-week treatment period. Dose increases were permitted after weeks 1 and 2; switching to BID was allowed after week 2, if needed. Measurements included changes in pain and sleep scores (0–10 scale), quality of life (QOL) scores (physical and mental component summaries [PCS and MCS, respectively] of the 36-Item Short-Form Health Survey instrument), and patient and clinician assessments of current treatment based on a 9-point scale ranging from −4 to +4.

Results:

One hundred forty-eight older patients (mean [SD]age, 73.4 [5.5] years) began treatment with P-ERMS; 86 (58.1%) of those patients completed the study. Pain and sleep scores significantly improved (decreased) from baseline to week 4 (7.4 vs 5.0 and 5.0 vs 3.2, respectively; both, P < 0.001). PCS and MCS scores significantly improved (increased) from baseline (27.7 vs 31.6 and 37.6 vs 40.8, respectively; both, P < 0.05), as did patient and clinician global assessments (−1.2 vs 1.1 and −1.5 vs 1.4; both, P < 0.001). Results found in these older patients were similar to those observed in the younger patients (aged ≤65 years). A majority (71.4%) of the older patients remained on QD administration and took significantly lower mean daily doses than younger patients (77.0 vs 105.2 mg/d, respectively; P = 0.001). The dropout rate for the subgroup was 41.1%, which was similar to that reported in previous studies in mixed-age populations taking other extended-release morphine formulations. Of the patients who discontinued (n = 60), adverse events (AEs) were the most prevalent reason (n = 29). The most common treatment-related AEs were constipation (19.6%) and nausea (9.5%).

Conclusions:

This subgroup analysis of a previously published study revealed that the older patients in that study who were receiving P-ERMS for persistent, moderate-to-severe, inadequately controlled, nonmalignant pain who completed the study attained significant improvements in pain, sleep, and QOL scores compared with baseline. Patient and clinician satisfaction with treatment increased significantly from baseline to study end. Older patients utilized significantly lower mean daily doses than younger patients (P < 0.001), and >70% remained on a QD administration regimen for the duration of the study.Key Words: analgesia, KADIAN, morphine, nonmalignant pain, persistent pain     

鞘内注射新斯的明或(和)吗啡对大鼠切口疼痛的影响

目的研究鞘内注射 (IT)吗啡或 (和 )新斯的明在大鼠切口疼痛模型中是否具有超前镇痛作用。方法雄性SD大鼠 6 4只 ,根据吗啡或 (和 )新斯的明的不同用法随机分为八组 (每组 8只 )。分别于术前、术后 2h、2 4h、4 8h、72h、96h、12 0h、14 4h以累积疼痛评分、vonFrey细丝法 (机械性痛觉过敏 )、热辐射法 (热痛觉过敏 )观察疼痛行为变化。结果与假手术组比较 ,在术后 2h和术后 2 4h、4 8h ,对照组大鼠的累积疼痛评分明显升高 (P <0 .0 1) ,热刺激缩爪潜伏期明显缩短 (P <0 .0 1) ,vonFrey纤毛刺激缩爪阈值明显降低(P <0 .0 1) ;与对照组比较 ,各用药组的累积疼痛评分均明显降低 (P <0 .0 1) ,热刺激缩爪潜伏期均明显延长 (P <0 .0 1) ,vonFrey纤毛刺激缩爪阈值均明显增加 (P <0 .0 1) ;上述指标在各用药组之间比较均无显著性差异。在术后第 96～ 14 4h ,对照组与假手术组比较 ,vonFrey纤毛刺激缩爪阈值仍存在统计学差异 (P <0 .0 1) ,其他指标各组之间比较均无显著性差异 (P >0 .0 5 )。结论在大鼠切口疼痛模型中 ,术前或术后单次IT新斯的明或 (和 )吗啡仅提供术后早期镇痛作用 ,而无超前镇痛作用。     

心外科术后吗啡与芬太尼患者自控镇痛效果观察

目的观察吗啡和芬太尼患者自控镇痛 (PCIA)用于心外科术后疼痛康复的疗效和安全性。方法将 70例心脏手术患者随机分为吗啡组和芬太尼组 ,术后在ICU病房用PCIA进行疼痛康复 ,观察镇痛起效时间、效果及满意率 ,以及 2 4h、48h和 72h生命体征及恶心、呕吐等副作用。结果两组患者的镇痛效果及满意率无显著性差异 ,生命体征均平稳 ,但芬太尼组的起效时间明显短于吗啡组 (P <0 .0 5 ) ,患者的恶心、呕吐次数明显少于吗啡组 (P <0 .0 5 )。结论吗啡和芬太尼PCIA均能安全地用于心外科术后患者急性疼痛的康复治疗 ,但芬太尼PCIA明显比吗啡PCIA起效快 ,恶心、呕吐副作用少。     

Use of a prophylactic antiemetic with morphine in acute pain: randomised controlled trial

Objective

The aim of this study was to compare the incidence of nausea and vomiting in patients with acute pain treated with morphine along with prophylactic metoclopramide or placebo.

Method

A randomised controlled trial was carried out on patients requiring morphine for acute pain in the emergency department (ED) setting. Children under the age of 12, patients who had been vomiting or had already received prehospital analgesia, and those unable to give consent were excluded. All patients were given either metoclopramide (10 mg) or placebo (normal saline) followed by intravenous morphine. Pain scores (measured on a visual analogue scale) before and after morphine administration, all incidents of nausea or vomiting, the dose of morphine, and the patients'' demographic data were recorded. Fisher''s exact test was used for comparing the two groups of patients.

Results

A total of 259 patients were recruited. There were 123 patients in the metoclopramide group (age range 15–94 years; median age 53) and 136 patients in the placebo group (age range 17–93 years; median age 52.5). The overall incidence of nausea and vomiting in the whole study population was 2.7%, (1.6% in the metoclopramide group and 3.7% in the placebo group). The difference between the two groups was not statistically significant (Fisher''s exact test = 0.451; p = 0.3; z‐test statistic = 1.02; 95% CI –6% to 2%).

Conclusion

When intravenous morphine is administered for acute pain, the overall incidence of nausea and vomiting is low, regardless of whether these patients are given prophylactic metoclopramide or not.