A randomized, double-blind comparison of the effects of interpleural bupivacaine and saline on morphine requirements and pulmonary function after cholecystectomy

The effect of interpleural bupivacaine and saline placebo on morphine requirements and pulmonary function after cholecystectomy was investigated. Twenty-six patients were randomly assigned on postoperative day 1 to receive either 20 ml preservative-free saline (group 1) or 20 ml 0.5% bupivacaine with epinephrine, 5 micrograms/ml (group 2) through an interpleural catheter. Adequacy of pain relief was determined by the amount of morphine used by the patient following interpleural injection. Morphine use via a patient-controlled analgesia (PCA) system was recorded for several hours before and after interpleural injection. All patients had a forced vital capacity (FVC) and FEV1 measurement immediately before and 1 h after interpleural injection. Mean hourly PCA morphine use ranged from 1.6 to 2.8 mg for the 6 h prior to interpleural treatment for groups 1 and 2. There was no difference in PCA use between the groups during this time. Group 1 patients did not reduce PCA morphine use after interpleural saline. Patients in group 2, however, significantly reduced PCA morphine use after interpleural bupivacaine. Mean PCA morphine use for group 2 was 0.38 +/- 0.15 mg/h (mean +/- SE) (81% reduction vs. control) for the first 2 h after bupivacaine (P less than 0.05). Mean PCA use in group 2 was 0.52 +/- 0.2 mg/h (73% reduction vs. control) for the third hour after bupivacaine (P less than 0.05). At the fourth and fifth hours after bupivacaine injection, mean PCA morphine use was not significantly different from that in group 1. FVC and FEV1 did not improve after interpleural saline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraperitoneal Versus Interpleural Morphine or Bupivacaine for Pain after Laparoscopic Cholecystectomy

Background: Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves. This study was designed (1) to examine a novel route of opioid administration, the intraperitoneal injection; (2) to compare this to interpleural application, and (3) to compare opioid with local anesthetic effects under both conditions.

Methods: At the end of laparoscopic cholecystectomy, 110 patients received the following injections in a double-blind, randomized manner: Group 1 (n = 18) was given intraperitoneal morphine (1 mg in 20 ml saline) and 20 ml intravenous saline. Group 2 (n = 17) received intraperitoneal saline and 1 mg intravenous morphine. Group 3 (n = 15) received 20 ml 0.25% intraperitoneal bupivacaine and intravenous saline. Group 4 (n = 20) received interpleural morphine (1.5 mg in 30 ml saline) and 30 ml intravenous saline. Group 5 (n = 20) received interpleural saline and 1.5 mg intravenous morphine. Group 6 (n = 20) received 30 ml 0.25% interpleural bupivacaine and intravenous saline. Postoperative pain was assessed using a visual analog scale, a numeric rating scale, and the McGill pain questionnaire. Pain localization, supplemental analgesic consumption, vital signs, and side effects were recorded for 24 h.

Results: Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy (P > 0.05, Kruskal-Wallis test), whereas interpleural bupivacaine was effective (P < 0.05, Kruskal-Wallis test, up to 6 h postoperatively) but not intraperitoneal bupivacaine (P > 0.05, Kruskal-Wallis test). Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h, about half of the patients complained of shoulder pain, which was rated "low" by about one-third of all patients. No significant side effects occurred.     

Post-cholecystectomy pulmonary function following interpleural bupivacaine and intramuscular pethidine

Twenty-four patients who were to undergo cholecystectomy were randomised into two groups, one to receive postoperative analgesia with interpleural bupivacaine, 20 ml of a 0.5% solution with adrenaline 5 micrograms/ml, and the other to receive intramuscular pethidine, 1 mg/kg. Preoperative and postoperative pulmonary function, postoperative pain scores, and days from operation to hospital discharge were recorded and statistically compared. There was no significant difference in pain scores, nor in days to discharge; however, postoperative pulmonary mechanics were significantly poorer in the interpleural group. A hypothesis to explain the differences is offered.     

Continuous interpleural infusion of bupivacaine for postoperative analgesia after surgery with flank incisions: a double-blind comparison of 0.25% and 0.5% solutions.

Postoperative analgesia, as assessed by visual analogue scale scores (0-10) and patient-controlled analgesia morphine requirements, pulmonary function (forced vital capacity and forced expiratory volume in 1 s), and plasma bupivacaine concentrations were studied in patients receiving interpleural blockade with bupivacaine after surgery with a flank incision. Two groups of 10 patients received either 0.5% or 0.25% bupivacaine, both with epinephrine (5 micrograms/mL). Pain relief was initiated when patients had visual analogue scale scores greater than or equal to 4. Patients received 21 mL of bupivacaine 0.25% or 0.5% in a double-blind fashion. One hour later, a continuous infusion of 5 mL/h of the study solution was started. At the same time, patient-controlled analgesia became accessible to the patients. The onset time of pain relief and the area under the visual analogue scale score-time curves over the first 8 h were similar in both groups. Patient-controlled analgesia morphine use was also similar in the 0.25% (21.3 +/- 14.6 mg) and 0.5% (21.0 +/- 16.0 mg) groups (mean +/- SD). In both groups, forced vital capacity and forced expiratory volume in 1 s improved significantly within 60 min (P less than 0.05). Peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC) over 24 h were higher (P less than 0.001) in the 0.5% group (Cmax, 1.47 +/- 0.37 micrograms/mL; AUC, 1511 +/- 323 micrograms.mL-1.min) than those in the 0.25% group (Cmax, 0.55 +/- 0.22 micrograms/mL; AUC, 680 +/- 118 micrograms.mL-1.min) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)     

Steady-state pharmacokinetics of interpleural bupivacaine in patients after cholecystectomy

Venous plasma concentrations of bupivacaine were determined in eight cholecystectomy patients following multiple interpleural bolus instillations of bupivacaine 20 ml 0.5% with adrenaline (5 mg/l) administered at six- to eight-hour intervals. The mean steady-state peak plasma concentration was 2.3 mg/l (range 1.2-3.1 mg/l); however, in three of the eight patients peak plasma concentrations were greater than 3 mg/l. The mean accumulation ratio was found to be 1.6 (range 0.99-2.49), with steady-state occurring within the first 24 hours of drug administration. Mean apparent systemic plasma clearance was 0.16 +/- 0.07 l/kg/h with a mean terminal half-life of 5.8 +/- 2.3 hours measured at steady-state, values which were not significantly different (P greater than 0.05) from those values obtained following single interpleural bolus dose administration.     

Interpleural or thoracic epidural analgesia for pain after thoracotomy. A double blind study

The analgetic effect of bupivacaine given epidurally or interpleurally after thoracotomy was investigated in a randomized, double blind, placebo controlled study. 32 patients with both an epidural and an interpleural catheter, were randomized to receive either interpleural or epidural analgesia. The interpleural group was given bupivacaine 5 mg ml^-1 with 5 microgram epinephrine as a 30 ml interpleural bolus, followed by a continuous infusion starting at a rate of 7 ml per hour and epidurally a bolus of 0.9% NaCl followed by a continuous infusion of 0.9% NaCl. The epidural group was given bupivacaine 3.75 mg–ml^-1 with 5 microgram epinephrine as a 5 ml epidural bolus, followed by a continuous infusion starting at a rate of 5 ml per hour and interpleurally a bolus of 0.9% NaCl followed by a continuous infusion of 0.9% NaCl. The draining tubes were clamped during the injection of the interpleural bolus and 15 min afterwards. Adequacy of pain relief was evaluated with the Prins–Henry pain scale. Morphine requirement was registered, there was no difference between the groups in painscores or need for additional morphine.     

Bilateral interpleural versus lumbar epidural bupivacaine-morphine analgesia for upper abdominal surgery

This randomized study was designed to compare the effectiveness of bilateral interpleural analgesia with lumbar epidural analgesia, on postoperative pain relief in upper abdominal surgery. The studied patients were randomely allocated into either interpleural group "IP" (n = 15) or epidural group "EP" (n = 15). In "IP" group, preanesthetic bilateral interpleural block was done using a mixture of bupivacaine 0.5% (0.8 mg/kg) and 2 mg morphine diluted to 50 ml saline for each side. In "EP" group, the same mixture-diluted in 20 ml saline-was injected in the epidural space (L2-3). The general anesthetic technique was the same in both groups. Hemodynamic, gasometric, verbal pain score (VPS) values and complications were compared in both techniques. Heart rate (HR) and mean arterial pressure (MAP) readings were in the accepted normal range in the perioperative period although significant lower readings were detected in "EP" group. No significant differences were displayed in blood gasometric variables between the two groups. There were considerable level of analgesia in both groups in the postoperative period although "EP" analgesia was superior to "IP". More pain free patients (9 versus 4) and significant lower consumption of nalbuphine were detected in "EP" group. The results of this study indicate that bilateral "IP" analgesia may offer a satisfactory analgesia for upper abdominal surgery when the use of other analgesic techniques may be contraindicated.     

Combined intrathecal morphine and bupivacaine for cesarean section

The effects of adding 0.2 mg preservative-free morphine sulfate in 0.2 ml solution to hyperbaric spinal bupivacaine were evaluated in a double-blind randomized prospective study of 34 patients undergoing elective repeat cesarean section. In the control patients (n = 17), 0.2 ml saline instead of morphine was added to bupivacaine. The intrathecal morphine significantly improved intra- and postoperative analgesia, e.g., 82% of patients given morphine compared with 41% of the control patients did not require analgesic supplementation to the spinal anesthesia during surgery; postoperatively, the former patients did not request additional analgesia for 27 +/- 0.7 hours (mean +/- SEM) compared with 2 +/- 0.3 hours in the control patients. Neonatal condition was not adversely affected by this small dose of morphine administered 11 +/- 1 minutes before delivery. Combining 0.2 mg morphine with hyperbaric spinal bupivacaine for cesarean section is a safe and effective method of improving intraoperative pain relief and providing adequate prolonged postoperative analgesia.     

Intrapleural catheter analgesia in patients with multiple rib fractures

Patients with multiple rib fractures often suffer from severe pain that impairs their respiratory performance. The effect of interpleural administration of bupivacaine (20 ml 0.25% every 4 h) for pain management was evaluated in ten patients. The initial interpleural injection resulted in significant pain relief and improvement of arterial oxygen tension. Two patients needed additional i.v. injections of opioids (piritramide 15-22.5 mg/24 h). In one patient a small asymptomatic pneumothorax was observed following placement of the catheter, which resolved spontaneously. No other complications were reported. In an intraindividual comparison, bupivacaine alone and bupivacaine plus epinephrine 1:200,000 were compared with regard to pharmacokinetics of bupivacaine, analgesic effect, side effects, and respiratory performance. The addition of epinephrine yielded only minor advantages from a pharmacokinetic point of view (median peak concentration of bupivacaine 1.8 micrograms/ml vs 2.0 micrograms/ml for bupivacaine alone). The quality and duration of analgesia and the effects on respiration were not influenced by epinephrine. The heart rate was significantly higher and the blood pressure significantly lower when epinephrine was added to the solution. Nevertheless, these differences were too small to be of clinical importance. Even though maximum total plasma concentrations of bupivacaine above 2 micrograms/ml were found in some patients, there were no signs of CNS toxicity, most probably because of the increased protein binding of bupivacaine following trauma. Accordingly, the maximum free plasma concentrations in all patients were below the threshold level of 0.24 micron/ml. We therefore conclude tht interpleural administration of bupivacaine could be a valuable means of pain relief in patients with multiple rib fractures, providing no severe pulmonary contusions or concomitant injuries are present.     

Postoperative analgesia using caudal morphine in pediatric surgery: randomized double-blind study compared with bupivacaine

Morphine and bupivacaine have been administered caudal via to 28 children between 2 and 12 years old for the postoperative pain treatment. All of them were submitted to general anesthesia and randomly divided into 3 groups depending on the drug administered caudal via. a) Morphine group (n = 10): morphine chlorhydrate 50 micrograms/kg (0.5 ml/kg of morphine solution 100 micrograms/ml). b) Bupivacaine group (n = 10): bupivacaine 0.5%, 2.5 mg/kg. c) Control group (n = 8): no drug administered. Pain evaluation was made on the basis of physiological and clinical data. In the morphine group, the postoperative time until analgesia was required 20 +/- 5 hours and analgesia has been significantly better (p less than 0.001) than bupivacaine and control group. The number of analgesic drug needed during the postoperative 24 first hours was also less in morphine group. No differences on postoperative complications were seen among the 3 groups and no case of respiratory depression was observed. It is concluded that epiduro-caudal morphine provides effective and prolonged analgesia and can be safely used for postoperative pain treatment in pediatric urologic surgery. However, we believe, that larger series of patients will provide better information of its efficacy and other side effects.     

Interpleural bupivacaine for analgesia during chest drainage treatment for pneumothorax. A randomized double-blind study

The ability of interpleural analgesia to reduce the pain caused by an indwelling chest drain was evaluated in 22 patients treated for spontaneous pneumothorax. Intermittent 8-hourly bolus injections of 20 ml bupivacaine 0.5% with epinephrine were compared with placebo in a randomized double-blind fashion. Visual analogue pain scale (VAS) scores were registered after the 1st, 2nd, 4th, 7th and 10th injections. The scores were significantly lower in the bupivacaine group at 5, 15, 30 and 60 min after the first injection. No significant differences in pain scores were found after 4 or 8 h. Pain scores in the bupivacaine group were also reduced after the 2nd, 4th, 7th and 10th injections, but compared with placebo the differences were significant only after the 2nd and 7th injections. Parenteral morphine consumption was not significantly lower in the bupivacaine group. Arterial blood gases were unaffected by the treatment in both groups. It is concluded that interpleural analgesia using bupivacaine given as bolus injections at 8-h intervals significantly reduces the pain caused by a chest drain within 5 min of injection, but the duration of pain relief is less than 4 h.     

Bilateral interpleural analgesia in a patient with multiple myeloma]

The case of one patient with multiple myeloma and thoracic pain during myeloptysis is described. Bilateral interpleural analgesia was accomplished with 10 ml of 0.375% bupivacaine with adrenaline (5 micrograms/ml) in both hemithorax and bilateral infusion at a rate of 3 ml/h started immediately and maintained during 24 hours. Analgesia was then obtained by means of a bolus pattern 10 ml/6 h until myeloptysis finished. Analgesic effectiveness was evaluated through visual analogue scale (VAS). Plasmatic levels of bupivacaine were found below toxic levels; maximum concentration was (1.12 microgram/ml) at the steady state (5 x t 1/2). Difficulty in treatment of pain and utility of interpleural analgesia is suggested.     

Combined morphine-bupivacaine caudals for reconstructive penile surgery in children: systemic absorption of morphine and postoperative analgesia

We wished to determine if the addition of a small dose of morphine (0.05 mg.kg-1) to a caudal solution of 0.25% bupivacaine could extend the duration of analgesia after major reconstructive penile surgery and also to measure the systemic absorption of morphine after caudal injection. Thirty children undergoing reconstructive penile surgery received a caudal injection of 0.25% bupivacaine 0.75 ml.kg-1 with or without morphine 0.05 mg.kg-1. All patients awoke pain-free, but eight of the fifteen patients receiving bupivacaine alone required supplementary injections of opioid postoperatively, whereas none of the patients receiving the bupivacaine-morphine mixture required additional opioids. The incidence of side-effects was similar for the two groups. Morphine was absorbed rapidly after caudal injection to reach a peak plasma level of 21.2 (+/- 4.8) ng.ml-1 at ten minutes and then fell to 10.1 (+/- 3.8) ng.ml-1 at one hour and 4.1 (+/- 2.6) ng.ml-1 at three hours. These levels are low compared with plasma levels associated with systemic analgesia. We conclude that the extended duration of analgesia from morphine 0.05 mg/kg given caudally is due at least in part to specific spinal analgesia.     

Interpleural analgesia improves pulmonary function after cholecystectomy

The purpose of this study was to examine the effects of interpleural bupivacaine on analgesia and ventilatory capacity after cholecystectomy. Forty-two patients undergoing elective cholecystectomy were randomly assigned to two groups: one to receive interpleural administration of bupivacaine-adrenaline mixture (Group 1 = 22 patients) and the other standard administration of intramuscular meperidine (Group 2 = 20 patients) for postoperative pain relief. The intensity of pain was evaluated by a visual analogue scale (VAS) preoperatively as well as at 2, 8, 24 and 48 hr postoperatively. At the same time, FVC and FEV1.0 measurements were obtained for all patients. The group given interpleural bupivacaine had better pain relief with mean VAS of 0.6 +/- 0.9 (mean +/- SD) 1.1 +/- 1.4, 0.6 +/- 0.9 and 0.8 +/- 1.2 compared with 5.2 +/- 2.2, 5.8 +/- 2.7, 5.5 +/- 2.2 and 4.5 +/- 1.8 for patients receiving meperidine (P less than 0.001). The patients in Group 1 also had larger FVC and FEV than those in Group 2: FVC 22 +/- 14.5 per cent vs 32 +/- 15.2 per cent (P less than 0.005), FEV1.0 25 +/- 15.5 vs 38 +/- 14.8 per cent (P less than 0.001) (mean +/- SD). We conclude that the interpleural analgesia can achieve better pain relief with greater ventilatory capacity than a standard analgesic regimen in the first two days after cholecystectomy.     

Interpleural analgesia for attenuation of postoperative pain after hepatic resection*

We performed a prospective randomised trial to evaluate the analgesic efficacy of interpleural analgesia in patients undergoing hepatic resection. The control group (n = 25) received multimodal analgesia with intravenous morphine patient‐controlled analgesia; in addition, the interventional group (n = 25) received interpleural analgesia with a 20‐ml loading dose of levo bupivacaine 0.5% followed by a continuous infusion of levobupivacaine 0.125%. Outcome measures included pain intensity on movement using a visual analogue scale over 24 h, cumulative morphine and rescue analgesia requirements, patient satisfaction, hospital stay and all adverse events. Patients in the interpleural group were less sedated and none required treatment for respiratory depression compared to 6 (24%) in the control group (p< 0.01). Patients in the interpleural group also had lower pain scores during movement in the first 24 h. Patients’ satisfaction, opioid requirements and duration of hospital stay were similar. We conclude that continuous interpleural analgesia augments intravenous morphine analgesia, decreases postoperative sedation and reduces respiratory depression after hepatic resection.     

Distribution of local anesthetics injected into the interpleural space, studied by computerized tomography

Twenty-one patients were given interpleural analgesia for postoperative pain relief after cholecystectomy, or renal or breast surgery. The patients were classified randomly into two groups: an interpleural injection of 20 ml of 0.375% bupivacaine mixed with 10 ml contrast medium was given to 11 patients in the supine position, and 10 in the lateral position. The patients remained in this position for 1 h. There was no significant difference in the rostrocaudal distribution of the contrast on computerized tomography taken 20 min later: Th3-L1 in the supine group vs. Th5-L1 in the lateral group. In the supine group the mean level of contrast medium reached significantly higher medially along the mediastinum (51 +/- 11 mm) than laterally (27 +/- 11 mm).     

Effects of interpleurally administered bupivacaine 0.5% on opioid analgesic requirements and endocrine response during and after cholecystectomy: a randomized double-blind controlled study

In 30 patients undergoing cholecystectomy, a randomized double-blind saline-controlled study was performed using interpleural 0.5% bupivacaine with or without epinephrine (5 micrograms.ml-1) in combination with 0.8% halothane inspired concentration in oxygen. The aim of the study was to investigate whether interpleural 0.5% bupivacaine could decrease the intraoperative opioid requirements and attenuate the metabolic endocrine response to surgical stress. Patients were randomly allocated to one of three groups: Group 1: 0.5% bupivacaine; Group 2: 0.5% bupivacaine with epinephrine (5 micrograms.ml-1); and Group 3: saline. The interpleural catheter was inserted after induction of anesthesia in the spontaneously breathing patient. The study drug was injected 30 min prior to surgery. Peak plasma bupivacaine concentrations in the respective groups were 1.30 +/- 0.78 and 1.16 +/- 0.48 micrograms.ml-1. In all patients concentrations were below suggested convulsive level. Two patients in Group 1 and two in Group 2 required intraoperative fentanyl (0.1 mg each). In contrast, eight patients in the saline group received an average of 0.21 mg (range 0.1 +/- 0.4 mg) fentanyl (P less than 0.05). Postoperatively, a second dose of the study drug was given. Subsequently, pain was assessed using a visual analog score and a verbal rating scale. Pain scores decreased significantly 30 min after the interpleural injection in both bupivacaine groups and remained unchanged in the saline group (P less than 0.05). Pain management by means of interpleural bupivacaine was successful in 17 of the 20 patients. In the saline group seven out of ten patients needed additional analgesics (P less than 0.05). Cortisol levels increased in response to surgery in all groups: maximum levels in Groups 1, 2 and 3 were: 1.09 +/- 0.29, 1.11 +/- 0.20 and 1.19 +/- 0.16 mumol.l-1, respectively. Plasma glucose concentrations increased significantly in all groups: maximum levels in Groups 1, 2 and 3 were: 7.6 +/- 1.3, 7.3 +/- 1.7 and 8.3 +/- 1.7 mmol.l-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative analgesia with epidural morphine after hip operations (author's transl)

80 patients undergoing hip surgery under lumbar epidural block have been studied (double blind) for postoperative analgesia. There were 4 groups, of 20 patients each, who received a single epidural injection of 0 mg, 2 mg or 4 mg morphine in 1 ml of saline added to 6 ml bupivacaine 0.5% or 4 mg morphine in 6 ml saline. In the morphine groups analgesia lasted between 37 and 50 hours. No neurological side-effects or severe respiratory depression have was observed; but a significant rise of paCO2 was found. Other side-effects were nausea/vomiting and the need for catheterisation in about 50% of patients. We conclude, that the indications for epidural analgesia with morphine have to be chosen carefully.     

Continuous epidural infusion of bupivacaine and morphine for postoperative pain relief

Forty-five patients admitted to the intensive care unit following thoracic or abdominal surgery received continuous epidural infusion of bupivacaine and morphine for 48 hours. During the first 10 hours, the patients received 0.25% bupivacaine solution with 0.005% morphine at the rate of 4 ml.h-1, and bupivacaine concentration was decreased to 0.125% with the same morphine concentration. The mean infusion rate of bupivacaine during 48 hours was 0.12 +/- 0.03 (SD) mg.kg-1.h-1 and that of morphine was 4.0 +/- 1.0 micrograms.kg-1.h-1. Thirty-one patients (69%) complained no pain on deep breathing at 24 hours and 33 patients (74%) required no other type of analgesics during this study. The mean plasma bupivacaine concentration was 0.6 +/- 0.3 microgram.ml-1 at 48 hours. Hypotension defined as systolic arterial pressure below 90 mmHg and itching were observed in 15 patients (33%), but no other severe side effects were noted. Continuous epidural infusion of bupivacaine and morphine mixture for 48 hours postoperatively provided effective pain relief with a low incidence of side effects.     

Effects of thoracic paravertebral block with bupivacaine versus combined thoracic epidural block with bupivacaine and morphine on pain and pulmonary function after cholecystectomy

Twenty patients undergoing elective cholecystectomy via a subcostal incision were randomized in a double-blind study to either thoracic paravertebral blockade with bupivacaine 0.5% (15 ml followed by 5 ml/h) or thoracic epidural blockade with bupivacaine 7 ml 0.5% + morphine 2 mg followed by 5 ml/h + 0.2 mg/h, respectively for 8 h postoperatively. Mean initial spread of sensory analgesia on the right side was the same (Th3,4-Th11 versus Th2,6-Th11), but decreased (P less than 0.05) postoperatively in the paravertebral group. All patients in the epidural group had bilateral blockade, compared with three patients in the paravertebral group. In both groups only minor insignificant changes in blood pressure and pulse rate were seen postoperatively. Pain scores were significantly higher in the paravertebral group, as was the need for systemic morphine (P less than 0.05). Pulmonary function estimated by forced vital capacity, forced expiratory volume and peak expiratory flow rate decreased about 50% postoperatively in both groups. In conclusion, the continuous paravertebral bupivacaine infusion used here was insufficient as the only analgesic after cholecystectomy. In contrast, epidural blockade with combined bupivacaine and low dose morphine produced total pain relief in six of ten patients.