Intraoperative Remifentanil Infusion Does Not Increase Postoperative Opioid Consumption Compared with 70% Nitrous Oxide

Background: Remifentanil is commonly used to replace nitrous oxide in general anesthesia to avoid the side effects of the latter. However, there are reports that intraoperative remifentanil infusion can lead to acute opioid tolerance. In this study, the authors tried to determine the dose of remifentanil comparable in efficacy to 70% nitrous oxide and to evaluate its effect on postoperative pain and morphine consumption after colorectal surgery using isoflurane anesthesia.

Methods: Sixty adult patients undergoing open colorectal surgery were randomly assigned to receive either remifentanil or 70% nitrous oxide along with isoflurane anesthesia. After morphine analgesia titration in the postanesthesia care unit, patient-controlled analgesia was commenced. Morphine consumption and pain were scored at rest and during cough or movement for 24 h.

Results: The mean remifentanil infusion rate was 0.17 [mu]g [middle dot] kg-1 [middle dot] min-1. The median visual analog pain score on arrival in the postanesthesia care unit was 1 (0-10) in the nitrous oxide group and 3 (0-9) in the remifentanil group (P < 0.05). Otherwise, there was no difference in pain scores at 5, 10, and 15 min and no difference in the total morphine consumption during the stay in the postanesthesia care unit. The two groups had similar total morphine consumption in the first 24 h and pain scores at rest and during movement. The incidence of postoperative nausea and vomiting was 10% in both groups. There was no difference in the sedation scores.     

A Comparison of Remifentanil and Morphine Sulfate for Acute Postoperative Analgesia after Total Intravenous Anesthesia with Remifentanil and Propofol

Background: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized micro-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol.

Methods: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 micro gram [center dot] kg sup -1 [center dot] min sup -1 remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 micro gram [center dot] kg sup -1 [center dot] min sup -1 and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed.

Results: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] >or= to 8 breaths/min and pulse oximetry >or= to 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 micro gram [center dot] kg sup -1 [center dot] min sup -1 (range, 0.05-0.23 micro gram [center dot] kg sup -1 [center dot] min sup -1), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, >or= to 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05).     

Epidural Morphine for Postoperative Pain Relief

In a clinical, double-blind study including 45 patients, who all underwent lower abdominal or urological surgery, the analgesic effect, latency and duration of epidural application of morphine were investigated in doses of 2 and 4 mg, respectively, compared to placebo. No significant difference was found in the effect of 2 mg morphine, compared to placebo. A significant decrease in pain score was found in the group of patients who received 4 mg morphine administered epidurally; however, this effect did not occur until 60 min after epidural administration. The effect of 4 mg morphine was found to be of long duration, as eight out of 15 patients did not require any supplementary analgesics within the first 24 h, compared to two out of 14 and three out of 15 patients, respectively, in the placebo and 2-mg groups.     

Epidural Morphine for Postoperative Pain Relief

Thirty-three patients were randomly assigned to two groups to study the analgesic potency, duration of action and side effects of epidural and intramuscular morphine after hip surgery. Two milligrams of preservative-free morphine chloride in 10 ml of normal saline in the epidural space was compared to 10 mg of intramuscularly administered morphine. There was a more rapid onset of action after intramuscular morphine. However, the quality of pain relief was substantially higher and the duration of action markedly longer after epidural morphine. The total dose required in the epidural group was 3.6 mg and in the intramuscular group 41 mg during the 15-h observation period. The side effects of epidural morphine were few and mild, the most embarrassing being urinary retention (20 %). Nausea and/or vomiting was less common after epidural morphine (20% versus 55%). Pruritus or respiratory depression which have been reported previously were not encountered. However, it is recommended that preservative-free solutions are used to avoid itching and that the patients are monitored, as respiratory depression may occur long after administration of epidural opiate.     

Intraoperative Nefopam Reduces Acute Postoperative Pain after Laparoscopic Gastrectomy: a Prospective,Randomized Study

Background

We assessed whether intraoperative nefopam would reduce opioid consumption and relieve postoperative pain in patients undergoing laparoscopic gastrectomy.

Methods

The 60 enrolled patients were randomly assigned to the control (n?=?32) or nefopam (n?=?28) group. All patients were blinded to their group assignment. We administered 100 ml of normal saline only (control group) or 20 mg of nefopam mixed in 100 ml normal saline (nefopam group) after anesthesia induction and at the end of surgery. The cumulative amount of fentanyl via intravenous patient-controlled analgesia (PCA), incidence of rescue analgesic medication, and numerical rating scale (NRS) for postoperative pain were evaluated along with the total remifentanil consumption.

Results

The mean infusion rate of remifentanil was significantly lower in the nefopam group (0.08?±?0.05 μg/kg/min) than in the control group (0.13?±?0.06 μg/kg/min) (P?<?0.001). Patients in the nefopam group required less fentanyl via intravenous PCA than those in the control group during the first 6 h after surgery (323.8?±?119.3 μg vs. 421.2?±?151.6 μg, P?=?0.009). Additionally, fewer patients in the nefopam group than in the control group received a rescue analgesic during the initial 6 h postoperatively (78.6 vs. 96.9%, P?=?0.028). The NRS measured while patients were in the post-anesthetic care unit was significantly lower in the nefopam group than in the control group (3.8?±?1.1 vs. 4.8?±?1.4, P?=?0.012). The subsequent NRS obtained after patients had been transferred to the general ward was comparable between the two groups during the following postoperative period.

Conclusions

Intraoperative nefopam decreased postoperative pain and opioid consumption in the acute postoperative period after laparoscopic gastrectomy. Hence, nefopam may be considered as a component of multimodal analgesia after laparoscopic gastrectomy.

     

Epidural Morphine for Postoperative Pain: Experience with 1085 Patients

A prospective study of the effect and side-effects of epidural morphine for pain relief in 1085 patients after thoracic, abdominal, urologic, or orthopaedic surgery was performed. Morphine chloride was diluted in saline or bupivacaine and administered through an epidural catheter placed at a segmental level appropriate for the type of surgery. The initial dose was 4 or 6 mg morphine and supplementary doses were given when needed to obtain complete freedom from pain during deep breathing or nursing care. The total dose of epidural morphine from end of surgery until the next morning varied from 4 to 18 mg. 97% of hip arthroplasty patients, 91% of prostatectomy patients and thoracotomy patients, 90% of patients after major lower extremity surgery and 88% of patients after laparotomy were completely satisfied with the postoperative course. For hip arthroplasty and major extremity surgery, an initial dose of 4 mg of epidural morphine was as effective as 6 mg. After prostatectomy, laparotomy, and thoracotomy, an initial dose of 6 mg gave significantly better effect than 4 mg. Pruritus occurred in 11%, nausea or vomiting in 34%, and respiratory depression in 0.9% of the total patient population. Urinary retention occurred in 42% of patients not having urinary catheters in place. Postoperative nausea or vomiting was more frequent in women than in men (P less than 0.001). There was a higher incidence of nausea or vomiting in men experiencing pain than in men who were completely pain-free after abdominal surgery (P less than 0.001). Respiratory depression was rare and occurred as a gradually decreasing respiratory rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pain Management: Part 1: Managing Acute and Postoperative Dental Pain

Safe and effective management of acute dental pain can be accomplished with nonopioid and opioid analgesics. To formulate regimens properly, it is essential to appreciate basic pharmacological principles and appropriate dosage strategies for each of the available analgesic classes. This article will review the basic pharmacology of analgesic drug classes, including their relative efficacy for dental pain, and will suggest appropriate regimens based on pain intensity. Management of chronic pain will be addressed in the second part of this series.     

Preperitoneal Bupivacaine Infiltration Reduces Postoperative Opioid Consumption,Acute Pain,and Chronic Postsurgical Pain After Bariatric Surgery: a Randomized Controlled Trial

Introduction

A multimodal pain treatment including local anesthetics is advised for perioperative analgesia in bariatric surgery. Due to obesity, bariatric surgery patients are at risk of respiratory complications. Opioid consumption is an important risk factor for hypoventilation. Furthermore, acute postoperative pain is an important risk factor for chronic postsurgical pain. In this study, we aimed to evaluate whether preperitoneal anesthesia with bupivacaine would reduce pain and opioid consumption after bariatric surgery.

Methods

One hundred adults undergoing laparoscopic bariatric surgery were randomized to receive either preperitoneal bupivacaine 0.5% or normal saline before incision. Postoperative opioid consumption, postoperative pain, and postoperative recovery parameters were assessed for the first 24 h after surgery. One year after surgery, chronic postsurgical pain and influence of pain on daily living were evaluated.

Results

Postoperative opioid consumption during the first hour after surgery was 2.8?±?3.0 mg in the bupivacaine group, whereas in the control group, it was 4.4?±?3.4 mg (p =?0.01). Pain scores were significantly reduced in this first hour at rest and at 6 h during mobilization on the ward. One year after surgery, the incidence of chronic postsurgical pain was 13% in the bupivacaine group versus 40% in the placebo group.

Conclusion

This study shows that preperitoneal local anesthesia with bupivacaine results in a reduction in opioid consumption and postoperative pain and seems to lower the incidence rate of chronic postsurgical pain after laparoscopic bariatric surgery.

     

Magnesium Increases Morphine Analgesic Effect in Different Experimental Models of Pain

Background: An excess of excitatory pathway activation via N-methyl-d-aspartate (NMDA) receptors has been described in neuropathic pain that responds poorly to morphine. However, in this situation, several published data sets show that coadministration of NMDA receptor antagonists restores the efficacy of opioids. Considering that magnesium behaves like an NMDA receptor antagonist, we investigated the effect of the combination of magnesium and morphine in experimental models of chronic and tonic pain.

Methods: Mechanical hyperalgesia was assessed with the paw-pressure test in mononeuropathic (chronic constrictive injury model) and diabetic rats. Behavioral reactions were scored in a model of inflammation induced by formalin. The animals were assigned to one of three groups according to the intraperitoneal pretreatment: magnesium (30 mg/kg x 3), magnesium (30 mg/kg), and saline. Before testing, morphine was injected intravenously in mononeuropathic (0.3 mg/kg) and diabetic rats (1 mg/kg) and by the subcutaneous route in rats with the formalin test (1.5 mg/kg).

Results: Magnesium alone induced a significant antihyperalgesic effect in mononeuropathic and diabetic rats after a cumulative dose of 90 mg/kg. Furthermore, it significantly increased morphine analgesia, regardless of the loading dose used (30 or 90 mg/kg) in the two models of neuropathic pain. In the formalin test, magnesium alone did not have a significant effect. However, in combination with morphine, it revealed the analgesic effect of this opiate.     

Double-blind, Multiple-dose Comparison of Buprenorphine and Morphine in Postoperative Pain

The analgesic profile and side-effects of buprenorphine 0.3 mg and morphine 10 mg intramuscularly were compared postoperatively in a double-blind, non-crossover, multiple-dose study. When the patient complained of moderate to severe postoperative pain after halothane-relaxant anaesthesia for upper abdominal surgery, the first test dose of either drug was given. Subsequent similar doses of buprenorphine 0.3 mg or morphine 10 mg were given when required (maximum ten doses). The first dose of both drugs gave an equal decrease in pain intensity, suggesting a relative potency of 33:1 for buprenorphine/morphine. A mean of 0.51 mg buprenorphine or 17 mg morphine had to be administered for satisfactory initial analgesia. Thereafter, the next analgesic dose was required a mean of 10.3 h after buprenorphine compared to 5.9 h after morphine ( P < 0.01). Significantly ( P < 0.01) fewer analgesic doses (mean 5.6) were needed in the buprenorphine group within the first 48 h postoperatively as compared to the morphine group (mean 7.3). A more pronounced mean decrease in the respiratory rate was observed after buprenorphine, but the mean minimum respiratory rates did not differ significantly from each other. Other effects of the two drugs on vital signs were similar. The incidence of other side-effects was fairly similar after both analgesics. The patients' subjective appraisal favoured buprenorphine.     

Sex- and Age-related Differences in Morphine Requirements for Postoperative Pain Relief

Background: Sex-related differences in the perception of pain and susceptibility to opioids remain a matter of debate. Intravenous morphine titration used to obtain pain relief in the immediate postoperative period is a unique clinical model for assessing the effect of sex on reported pain. Because of the wide variation in dose requirements for pain management, the authors conducted a prospective study in a large population and also assessed the effect of aging.

Methods: Intravenous morphine titration was administered as a bolus of 2 (body weight << 60 kg) or 3 mg (body weight > 60 kg) during the immediate postoperative period. The interval between each bolus was 5 min. The visual analog pain scale (VAS) threshold required to administer morphine was 30, and pain relief was defined as a VAS score of 30 or less. Data are expressed as mean +/- SD.

Results: Data from 4,317 patients were analyzed; 54% of the patients were male, and 46% were female. The mean morphine dose required to obtain pain relief was 11.9 +/- 6.8 mg or 0.173 +/- 0.103 mg/kg. Women had a higher initial VAS score (74 +/- 19 vs. 71 +/- 19; P < 0.001) and required a greater dose of morphine (0.183 +/- 0.111 vs. 0.165 +/- 0.095 mg/kg; P < 0.001). In contrast, no significant difference was noted in elderly (aged > 75 yr) patients (0.163 +/- 0.083 vs. 0.157 +/- 0.085 mg/kg).     

Effects of Single-Dose Preemptive Pregabalin and Intravenous Ibuprofen on Postoperative Opioid Consumption and Acute Pain after Laparoscopic Cholecystectomy

Purpose: Non-opioid medications as a part of multimodal analgesia has been increasingly suggested in the management of acute post-surgical pain. The present study was planned to compare the efficacy of the combination of pregabalin plus ?v ibuprofen. Methods: 58 patients were included in this prospective, randomized, double-blinded study. The pregabalin group (Group P, n = 29) received 150 mg pregabalin, the pregabalin plus ibuprofen group (Gropu PI, n = 29) received 150 mg pregabalin and 400mg ?v ibuprofen before surgery. Postoperative fentanyl consumption, additional analgesia requirements and PACU stay were recorded. Postoperative analgesia was performed with patient-controlled IV fentanyl. Results: VAS scores in the group PI were statistically lower at PACU, 1and 2 hours at rest, at PACU, 1, 2, 4, 12 and 24 hours on movement compared to the group P (P < 0.05). Opioid consumption was statistically significantly higher in the group P compared to the group PI (130.17 ± 60.27 vs 78.45 ± 60.40 μq, respectively, P < 0.001) and reduced in the 4th 24 hours by 55% in group PI. Rescue analgesia usage was statistically significantly higher in the group P than in the group PI (16/29 vs 7/29, respectively, P < 0.001). Four patient in the group PI did not need any opioid drug. Besides, PACU stay was shorter in the group PI than the group P (10.62 ± 2.38 vs 15.59 ± 2.11 min, respectively, P < 0.001). Conclusion: Preemptive pregabalin plus ?v ibuprofen in laparoscopic cholecystectomy reduced postoperative opioid consumption. This multimodal analgesic aproach generated lower pain scores in the postoperative period.     

Epidural Morphine by the Caudal Route for Postoperative Pain Relief

In order to detect the ability of epidural morphine, administered by the caudal route, to produce pain relief and in order to compare pain relief by this method with intramuscular injections of opiates, 90 patients scheduled for surgery below the umbilical level were studied. Four milligrams of preservative-free morphine in 10 ml normal saline was compared with intramuscular injections of opiates, using a visual analogue scale. The average pain score was significantly lower in the epidural group during the first 12 postoperative hours. In the epidural group, 38% required additional intramuscular injections during the first 12 h, whereas 86% of the patients in the intramuscular group received opiate injections. No patients developed respiratory depression. Side effects were more common in the intramuscular group than in the epidural group. It is concluded that epidural morphine by the caudal route is a better choice than intramuscular injections in controlling postoperative pain below the umbilical level.     

Experimental Cutaneous Pain Thresholds and Tolerance in Clinical Analgesia with Epidural Morphine

Ten patients experiencing significant analgesia from repealed low-dose morphine injections via an indwelling epidural catheter were studied. One group (n=5) with acute, postoperative pain was tested for changes in experimental cutaneous pain thresholds with and without clinical morphine analgesia. Three of these patients received intravenous naloxone. The analgesia was reversed in two. There was no significant alteration in any cutaneous modality, including pain, although the postoperative deep pain was relieved. This discrepancy might be explained by the existence of separate subpopulations of opiate receptors at the spinal cord level, which differentiate nociceptive input from the skin and from deep body structures. The other group (n = 5) of cancer pain patients with a permanent epidural catheter was monitored for long-term changes in clinical pain. Signs of tolerance were not seen with an observation period up to 6 weeks.     

A Comparison of Epidural Morphine and Epidural Bupivacaine for Postoperative Pain Relief

In 32 patients subjected to total hip replacement, postoperative pain relief was achieved by random treatment with either 5 mg of morphine in 10 ml of saline (n = 15) or 6–8 ml of 0.5% bupivacaine with epinephrine (n = 17), both drugs administered by the lumbar epidural route. In an additional group of 10 patients, post-traumatic thoracic or post-operative abdominal pain was relieved first by 4–6 ml of 0.5% bupivacaine with epinephrine and subsequently by 5 mg of morphine in 10 ml of saline, both drugs being administered by the thoracic epidural route. The duration of analgesia was significantly longer, on average, with morphine (28 h) than with bupivacaine (4.3 h) when the drugs were given by the lumbar route. Thoracic administration of morphine also resulted in a significantly longer duration of pain relief (on average 9.8 h) than that of bupivacaine (3.8 h). Morphine gave satisfactory pain relief in all cases. It was not associated with motor block, loss of sensitivity to temperature, touch, or pin-prick, or any signs of sympathetic block, as was the case with epidural bupivacaine. Plasma concentrations of morphine were not detectable 8 h after injection, though the patients still had pain relief. One case of delayed severe respiratory depression occurred 6 h after morphine injection via the thoracic route. Epidural morphine analgesia should therefore be reserved for patients in whom continual surveillance is possible, at least until more is known about the pharmacokinetics of narcotics in the epidural and subarachnoid space.