Esophageal blood flow in the rabbit: response to calcium channel blockers

Calcium channel blockers have recently been added to the therapeutic regimen for patients who have chest pain of esophageal origin. Although relief of symptoms has been reported, this has not always been associated with changes in esophageal contraction pressures or luminal pH. Myoischemia has been proposed as one possible mechanism for esophageal chest pain. We have investigated the effect of the calcium channel blockers verapamil, nifedipine, and diltiazem on esophageal blood flow in the rabbit model. Esophageal blood flow was measured three times in each rabbit with use of the radiolabeled microsphere technique after a 30-minute continuous infusion of (1) saline solution (baseline), (2) a low dose, and (3) a high dose of each agent. Esophageal mucosal blood flow significantly decreased with nifedipine but was unchanged with verapamil and diltiazem. Esophageal muscle blood flow significantly increased--approximately 100% after administration of each of the calcium channel blockers. Thus esophageal muscle blood flow is enhanced after administration of calcium channel blockers, and this may be one therapeutic mechanism of the calcium channel blockers in the relief of esophageal chest pain in some esophageal diseases.     

Epidural administration of midazolam with saline or bupivacaine for postoperative pain]

Postoperative pain relief and sedation with epidural midazolam-saline or midazolam-bupivacaine were studied in 46 patients after elective upper abdominal surgery. They were divided into 6 groups. In each group, 10 ml saline, 10 ml saline+midazolam 0.05 mg.kg-1, 10 ml saline+midazolam 0.1 mg.kg-1 (saline group), 0.25% bupivacaine 6 ml, 0.25% bupivacaine 6 ml + midazolam 0.05 mg.kg-1 or 0.25% bupivacaine 6 ml + midazolam 0.1 mg.kg-1 (bupivacaine group) was administered via epidural catheter for complaint of pain. For 120 minutes after epidural injection, blood pressure (BP), heart rate (HR), respiratory rate (RR), sedation score, and serum concentration of midazolam (conc midazolam) were evaluated. The time interval until next complaint of pain (pain relief time) was measured. In midazolam injected group, BP, HR, RR were not changed from preinjection value, but sufficient sedation was obtained and pain relief time was significantly prolonged compared with saline or bupivacaine injected group. Midazolam level was lower than that of sedation level. There were no significant differences between saline group and bupivacaine group, but the pain relief effect was slightly stronger in bupivacaine group. It is concluded that epidural saline - midazolam or 0.25% bupivacaine - midazolam is useful for postoperative pain relief after upper abdominal surgery.     

The interaction effect of perioperative cotreatment with dextromethorphan and intravenous lidocaine on pain relief and recovery of bowel function after laparoscopic cholecystectomy

Both dextromethorphan (DM) and IV lidocaine improve postoperative pain relief. In the present study, we evaluated the interaction of DM and IV lidocaine on pain management after laparoscopic cholecystectomy (LC). One-hundred ASA physical status I or II patients scheduled for LC were randomized into four equal groups to receive either: (a) chlorpheniramine maleate (CPM) intramuscular injection (IM) 20 mg and IV normal saline (N/S) (group C); (b) DM 40 mg IM and IV N/S (group DM); (c) CPM 20 mg IM and IV lidocaine 3 mg . kg(-1) . h(-1) (group L); or (d) DM 40 mg IM and IV lidocaine (group DM+L). All treatments were administered 30 min before skin incision. Analgesic effects were evaluated using visual analog scale pain scores at rest and during coughing, time to meperidine request, total meperidine consumption, and the time to first passage of flatus after surgery. Patients of the DM+L group exhibited the best pain relief and fastest recovery of bowel function among groups. Patients in the DM and L groups had significantly better pain relief than those in the C group. The results showed an additional effect on pain relief and a synergistic effect on recovery of bowel function when DM was combined with IV lidocaine after LC.     

氯诺昔康及曲马多用于妇科剖腹手术后病人自控镇痛的临床比较研究

目的 评价氯诺昔康及曲马多用于妇科剖腹手术后病人自控镇痛（PCA）的安全性及有效性。方法 60例在全麻下行开腹妇科手术的患者,随机双盲分为氯诺昔康组（L组）和曲马多组（Q组）。病人根据镇痛需要启动PCA泵（氯诺昔康每次1mg或曲马多每次12.5mg,锁定时间5分钟）,并由病人从疼痛程度差值（PID）、疼痛缓解程度（PAR）、疼痛缓解总和（TOTPAR）完成对疼痛的评分（VRS,口述描绘5组评分法）,并记录发生的副作用。结果 L组和Q组的TOTPAR无显著性差异,两组病人各时间点的PID和PAR的趋势相同,在病人镇痛总体印象评分中,L组镇痛满意的比例略高于Q组,但无统计学差异。Q组恶心与呕吐的发生率明显高于L组。结论 氯诺昔康用于妇科开腹手术后PCA的效应与曲马多接近,副作用少,适用于PCA。     

Piroxicam, Acetylsalicylic Acid and Placebo for Postoperative Pain

A double-blind comparison of the pain-relieving effect of piroxicam 5 and 10 mg, acetylsalicylic acid 648 mg and placebo was performed in 120 patients with moderate to severe pain on the morning after orthopedic surgery. The changes in pain intensity and pain relief during the 8 h following medication were recorded by a trained nurse observer. 67 % of the placebo-treated patients needed rescue drugs compared to 41% of the acetylsalicylic acid, 43% of the piroxicam 5 mg, and 45% of the piroxicam 10 mg treated patients. One to three hours after ingestion of the test drug, the piroxicam and the acetylsalicylic acid groups had significantly improved verbal rating pain intensity scores compared to placebo. In the overall assessment of pain relief at the end of the observation period, the patients' own assessment was significantly superior for acetylsalicylic acid and piroxicam 10 mg compared with placebo. In the observer's assessment of overall pain relief, placebo was significantly inferior to the three other groups. Thus piroxicam 5 mg and 10 mg give relief of pain after orthopedic surgery similar to that given by acetylsalicylic acid 648 mg. The pain-relieving effect of these drugs can be distinguished from placebo, but not from each other. They are not potent enough when pain is moderate to severe after orthopedic surgery.     

Do beta adrenergic receptor blockaders increase bupivacaine cardiotoxicity?

Bupivacaine is known to impair the electrophysiology of the heart as well as haemodynamic parameters. Administration of calcium channel blockers prior to bupivacaine enhances its cardiotoxicity. This study assessed the effects of bupivacaine at toxic dose in dogs with previous beta-adrenergic receptor blockade. It included 12 dogs anaesthetized with thiopentone, allocated in a control group (n = 6) receiving a bolus of bupivacaine (4 mg.kg-1) and a study group (n = 6) treated with the sequence propranolol (0.2 mg.kg-1) and bupivacaine (4 mg.kg-1), 15 min later. Infranodal conduction (HV conduction times and QRS durations) was worsened in both groups. Previous propranolol administration had no potentiating effects on these parameters. Conversely the latter was responsible of a greater decrease in heart rate, and increase in atrio-ventricular conduction time (77.9% vs 18.7%, p less than 0.05), as well as a more severe hypotension. Moreover, 3 out of the 6 animals in the study group suffered a cardiac arrest between the 5th and the 10th min. It is concluded that in anaesthetized dogs the cardiac and circulatory effects of a toxic dose of bupivacaine are increased in case of preexisting blockade of beta adrenergic receptors.     

Epidural diamorphine for post-caesarean pain: a dose response study

The effectiveness of postoperative pain relief and the frequency of side effects with three different doses of epidural diamorphine (2.0, 3.5 and 5 mg) was investigated. The study was carried out double-blind in 30 women undergoing awake elective caesarean section. Postoperative pain intensity was measured on a linear analogue scale. The time to onset of analgesia (TOA), time taken to reach a pain score of zero or become comfortable, and time to next analgesia (TNA) were not significantly different between groups. Three patients in the 2 mg group failed to achieve scores of zero but were comfortable. No nausea or vomiting was seen but the incidence of itching was 0, 30% and 80% in the 2.0, 3.5 and 5 mg groups respectively. We conclude that epidural diamorphine 2 mg is adequate for relief of post-caesarean pain and higher doses may increase the incidence of unwanted side-effects.     

Arrhythmia prophylaxis after aorta-coronary bypass. The effect of minidose propranolol

After aorta-coronary bypass grafting, 164 consecutive patients were randomized to receive propranolol 5 mg every 6 hours orally (n = 82) or to serve as control subjects (n = 82). All patients were receiving beta blockers preoperatively. There were no significant differences between the two groups. The incidence of sustained supraventricular (nonsinus) tachyarrhythmias was 23% in the control group and 9.8% in the treated group (p = 0.02). The incidence of ventricular arrhythmias was 15% in the control group and 2.4% in the treated group (p = 0.005). The overall difference in clinically important arrhythmias was 38% in the control group and 12.2% in the treated group (p = 0.0002). We conclude that low-dose oral propranolol in patients who were receiving beta blockers preoperatively is effective in reducing the incidence of clinically important arrhythmias occurring after aorta-coronary bypass grafting.     

Double-blind comparison of intravenous doses of dezocine, butorphanol, and placebo for relief of postoperative pain

The safety and efficacy of intravenous doses of dezocine (5 or 10 mg), butorphanol (1 mg), and placebo were compared in a double-blind study in 160 patients with moderate to severe postoperative pain. Analgesic efficacy was assessed for 6 hours after each dose. Mean pain relief scores were consistently higher, indicating greater pain relief, for the three active treatment groups than for the placebo group. The 10-mg dezocine dose was the most effective treatment, and 5 mg of dezocine was comparable to 1 mg of butorphanol. In the 2 hours after the first dose, 32% of the 10-mg dezocine group, 53% of the 5-mg dezocine group, 65% of the butorphanol group, and 88% of the placebo group withdrew from the study because of unsatisfactory pain relief. The differences in these percentages were statistically significant (P less than 0.05) between each active therapy group and the placebo group, and between the 10-mg dezocine group and the butorphanol group. Changes in degree of sedation were similar in the three active therapy groups. Adverse reactions were rare, mild, and equally distributed among the four treatment groups. We conclude that 10 mg of dezocine is superior to 1 mg of butorphanol, and that 5 mg of dezocine is as effective as 1 mg of butorphanol for the relief of moderate to severe postoperative pain.     

The effects of prolonged ambulation on labor with epidural analgesia

Ambulation during labor is becoming more popular, although its impact on the progress of labor and on pain intensity remains unclear. We wondered whether prolonged ambulation with epidural analgesia had a possible effect on duration of labor and pain. In this prospective, randomized trial, 61 parturients with uncomplicated term pregnancies were allocated to be recumbent (n = 31) or to ambulate (n = 30). Epidural analgesia was provided with intermittent administrations of 0.08% bupivacaine-epinephrine plus 1 microg/mL of sufentanil. Of the 30 women assigned to the ambulatory group, 25 actually walked. Their ambulating time was 64 +/- 34 min (mean +/- SD), i.e., 29% +/- 16% of the first stage. There were no differences between the two groups in the length of labor and in pain visual analog scale scores. However, the ambulatory group received smaller doses of bupivacaine (6.4 +/- 2.2 mg/h versus 8.4 +/- 3.6 mg/h; P = 0.01) and of oxytocin (6.0 +/- 3.7 mUI/min versus 10.2 +/- 8.8 mUI/min; P < 0.05). A greater ability to void was also found in the ambulatory group (P < 0.01). Although the duration of labor and pain relief was unchanged, these findings support that ambulation during labor may be advantageous. IMPLICATIONS: This study compared the duration of labor and pain relief between parturients receiving epidural analgesia who were ambulated or were recumbent. Whereas walking had no impact on either duration of labor or pain relief, it was associated with a reduction in both bupivacaine and oxytocin requirements.     

Application of sublingual buprenorphine in combination with naproxen or paracetamol for post-operative pain relief in cholecystectomy patients in a double-blind study

In a double-blind, placebo-controlled study in 125 patients undergoing a cholecystectomy, a comparison was made of the quality of post-operative pain relief during 'patient-controlled' intake of sublingual buprenorphine in combination with either rectally administered naproxen 1000 mg/24 h, paracetamol 4000 mg/24 h or a placebo. Results obtained in 97 patients were analysed. Five of these patients needed a rescue medication with morphine hydrochloride intramuscularly because of insufficient pain relief or because of nausea and vomiting. The quality of pain relief, as measured on a four-point scale, was comparable in all three groups throughout the study period and no significant differences became apparent. Only on the day of surgery (day 0) was intake of buprenorphine significantly greater in the placebo group (2.3 tablets/24 h) than in the naproxen and paracetamol groups (1.8 and 1.5 tablets/24 h, respectively). It is concluded that after cholecystectomy 'patient-controlled' intake of sublingual buprenorphine as a sole agent provides acceptable pain relief in about 80% of patients. More elaborate methods, such as intravenous patient-controlled analgesia, might be necessary to achieve good pain relief in the remainder of these patients.     

Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation

Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS. Received: 28 October 1999 Revised: 16 March 2000 Accepted: 29 September 2000     

Clonidine as an analgesic adjuvant to continuous paravertebral bupivacaine for post-thoracotomy pain

We prospectively evaluated the effect of clonidine as an adjuvant to bupivacaine for continuous paravertebral intercostal nerve block, measuring pain and sedation scores and pulmonary function tests. Thirty patients scheduled to undergo thoracotomy were randomized to receive either a bolus of 0.125% bupivacaine 2 mg/kg (group BUP) or 0.125% bupivacaine 2 mg/kg with clonidine 2 microg/kg (group BUP+CLO), followed by an infusion of 0.125% bupivacaine at 0.5 mg/kg/h, or 0.125% bupivacaine at 0.5 mg/kg/h with clonidine at 2 microg/kg/h, in respective groups, through a paravertebral intercostal catheter. Haemodynamic parameters, pain and sedation scores and pulmonary function tests were recorded at 6, 12, 24 and 48 hours after arrival in postoperative care unit. There were significantly lower pain scores at rest and on coughing in group BUP+CLO compared with group BUP (P <0.01). Multiple comparisons revealed a significant reduction in pain score at each time point (P<0.01), except at 12h to 24h, in group BUP+CLO. Sedation scores were significantly higher in group BUP+CLO compared with group BUP at each time point (all P<0.01). There was a linear effect of time on sedation score in group BUP whereas in group BUP+CLO, the effect was quadratic. Patients in the clonidine group had a higher incidence of hypotension (P < 0.01). There was no significant difference in pulmonary function between the groups. We conclude that using clonidine as an adjunct to bupivacaine for continuous paravertebral intercostal nerve block improves pain relief after thoracotomy, but hypotension and sedation are adverse effects interfering with its clinical application.     

Neurolysis using a carbohydrate polymer gel for the treatment of postoperative neuropathic pain

Abstract

Perineural and intraneural fibrosis is thought to be the main cause of failure of the many surgical treatments of neuropathic pain. We have used Adcon-T/N^® carbohydrate polymer gel for prevention of perineural fibrosis in several parts of the body. In this retrospective study, 54 patients who presented with postoperative neuropathic pain had microsurgical epineural neurolysis and relocation of a terminal neuroma. In 19 of them, the carbohydrate gel was applied at the same time. The mean follow-up was four years and the nerve distribution varied. Postoperative improvement in pain scores (visual analogue scale (VAS) and neuropathic pain scale inventory (NPSI)), sensitivity, overall improvement and satisfaction were equivalent in the two groups, with pain relief in about 80% of the patients. There was no significant beneficial effect in the carbohydrate gel group. Patients treated with this device had a higher infection rate (21 compared with 0, p = 0.01) and delayed wound healing (31.6 compared with 11.8, p = 0.2). We conclude that good long-term pain relief is obtained postoperatively independently of the addition of carbohydrate gel. There was a slight but not significant trend towards profound pain relief with the gel.     

Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled trial

BACKGROUND: Neuropathic pain in spinal cord injury is a common challenging therapeutic condition. The current study examines the analgesic effect of the sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord injury and the predictive role of concomitant evoked pain on pain relief with lidocaine. METHODS: Twenty-four spinal cord injury patients with neuropathic pain at or below the level of injury were randomized and completed a double-blind crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous and evoked pains were assessed using a visual analog scale and quantitative sensory testing. RESULTS: Lidocaine significantly reduced spontaneous pain in all patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P = 0.048) evoked pain, with no difference in number of responders (pain reduction > or = 33%) between the patients with (n = 6) and without (n = 5) evoked pain. Lidocaine significantly relieved both at-level and below-level neuropathic pain and decreased brush-evoked dysesthesia but not cold allodynia, pinprick hyperalgesia, or pain evoked by repetitive pinprick. CONCLUSIONS: Lidocaine reduced neuropathic pain at and below the level of injury irrespective of the presence or absence of evoked pain. Results are consistent with a central-acting effect of sodium channel blockers acting on neuronal hyperexcitability. Agents (such as anticonvulsants or antiarrhythmics) with sodium channel-blocking properties may be a treatment option for spinal cord injury pain.     

Comparison of oral controlled release morphine and epidural morphine in the management of postoperative pain

Oral controlled release morphine (CRM) was compared in a double-blind study with epidural morphine (EM) for postoperative pain relief in 20 patients undergoing knee arthrotomy under epidural anesthesia. Ten patients received 30 mg CRM orally and saline epidurally (CRM group), and ten patients received placebo tablets orally and 4 mg morphine epidurally (EM group), both at the time of skin incision and then every 8 hr for 48 hr during which patients evaluated pain intensity using a visual analog scale. Nine of the ten patients in the EM group had good relief of pain throughout the study period. Seven of the ten patients in the CRM group needed rescue analgesics within 6 hr of the initiation of the study (P less than 0.01). We conclude that CRM is not suitable for the control of early postoperative pain, whereas epidural morphine is excellent.     

Amlodipine reverses the elevation in [Ca2+]i and the impairment of phagocytosis in PMNLs of NIDDM patients

BACKGROUND: Patients with diabetes mellitus display an elevation in the basal levels of [Ca2+]i of polymorphonuclear leukocytes (PMNLs) and impaired phagocytosis. These derangements are due to the hyperglycemia of diabetes. Calcium channel blockers reverse these abnormalities both in in vitro studies and in diabetic rats. These observations suggest that calcium channel blockers may be useful in the treatment of patients with uncontrolled diabetes. The present study examined this issue. METHODS: A total of 32 normal subjects and 36 patients with uncontrolled noninsulin-dependent diabetes mellitus (NIDDM) were studied with and without treatment with amlodipine both in a cross-sectional and longitudinal design approach. RESULTS: In addition to the elevation in basal levels of [Ca2+]i and the impaired phagocytosis, there was also down-regulation of the mRNA of Fc gamma RIII receptors in the PMNLs of the diabetic patients. Treatment of the patients with a small dose of amlodipine (5 mg/day) corrected these abnormalities despite persistent hypoglycemia. This beneficial effect of nifedipine was noted as long as the therapy with the drug was maintained. CONCLUSION: The results show that the elevation in [Ca2+]i of the PMNLs is associated with down-regulation of the mRNA of their Fc gamma RIII receptors, which is at least, in part, responsible for the impaired phagocytosis. These derangements in the metabolism and function of the PMNLs are most likely responsible for the increased susceptibility of the diabetic patients to infection. Calcium channel blockers may be a beneficial adjunct therapy in patients with uncontrolled diabetes.     

Intrathecal morphine dose-response data for pain relief after cholecystectomy

We studied the effect of low-dose intrathecal morphine (0.00-0.20 mg) on pain relief and the incidence of side effects after cholecystectomy in 139 patients divided into eight groups according to intrathecal morphine dose: groups 1 (0.00 mg), 2 (0.04 mg), 3 (0.06 mg), 4 (0.08 mg), 5 (0.10 mg), 6 (0.12 mg), 7 (0.15 mg), and 8 (0.20 mg). Preservative-free morphine hydrochloride mixed in hyperbaric tetracaine solution was administered at the time of induction of spinal anesthesia just before surgery. Pain relief was significantly greater for the first 24 h in groups 3, 4, 5, 6, 7, and 8 than in group 1. The incidence of respiratory depression was significantly greater in groups 7 and 8 than in the other groups in the first 48 h. Vomiting occurred significantly more often in group 1 than in groups 2, 3, 4, and 5. Intraoperative cholangiography and the postoperative clinical course indicated no increase in tone of the sphincter of Oddi in any patient. We conclude that 0.06-0.12-mg intrathecal morphine is the best dose range for pain relief after cholecystectomy without respiratory depression and with the lowest incidence of vomiting or pruritus, or both.     

Intrathecal morphine for postoperative pain relief after transvaginal hysterectomy]

We studied the effect of a low-dose intrathecal morphine (0.1 or 0.2 mg) in postoperative pain relief and the incidence of side effects. Two hundred and fifteen patients scheduled for transvaginal hysterectomy were divided into 3 groups according to intrathecal morphine doses: M1 (morphine 0.1 mg N = 75), M2 (morphine 0.2 mg N = 69) and C (control N = 71). A standard mid-line lumbar puncture was performed using a 25-gauze needle in the L3/4 interspace. Preservative-free morphine hydrochloride mixed in hyperbaric tetracaine solution was administered intrathecally. Pain relief was significantly greater for the first 24 hrs in groups M1 and M2 compared with group C. Respiratory depression was not seen in any groups. The incidence of vomiting was about 40% in all groups. We conclude that intrathecal morphine 0.1-0.2 mg is useful for pain relief after transvaginal hysterectomy and accompanies no major side effects.     

Methylprednisolone intravenously 1 day after surgery has sustained analgesic and opioid-sparing effects

BACKGROUND: In previous studies on glucocorticoids for postoperative pain, the test drug has been given perioperatively, usually before measurement of baseline pain. In order to evaluate the time course and magnitude of the analgesic effect of a glucocorticoid in well-established postoperative pain, we compared methylprednisolone with ketorolac and placebo, after assessment of baseline pain on the first postoperative day. METHODS: This was a double-blind, single dose, randomized, parallel comparison of intravenous (i.v.) methylprednisolone 125 mg, ketorolac 30 mg as an active control, and placebo in 75 patients with moderate to severe pain 1 day after orthopaedic surgery. Outcome variables were pain intensity (0-100 VAS), pain relief (0-4 PAR) and rescue opioid consumption. RESULTS: Methylprednisolone was not significantly different from ketorolac and gave significantly lower pain intensity from 1 h (0-6 h, P < 0.02), and more pain relief 2-6 h after test drugs (P < 0.05) compared with placebo. After 24 h, pain intensity was lower in both active drug groups compared with placebo (methylprednisolone, P < 0.0001; ketorolac, P < 0.007). Number needed to treat (NNT) calculated from patients having more than at least 50% of maximum obtainable total pain relief during the first 6 h (>50%maxTOTPAR(6 h)) was 3.6 for methylprednisolone and 3.1 for ketorolac. Number needed to treat calculated from the percentage reporting at least 50% pain relief for at least 4 h (>50%PAR(4 h)) was 2.8 for both groups. Opioid consumption was significantly reduced for 72 h after methylprednisolone compared with ketorolac (P < 0.02) and placebo (P < 0.003). CONCLUSION: Methylprednisolone 125 mg i.v. 1 day after surgery gave similar early reduction of pain as i.v. ketorolac 30 mg. Less pain than placebo 24 h after methylprednisolone, and lower opioid consumption for 72 h compared with ketorolac and placebo indicate sustained analgesic effects of methylprednisolone.