First Dose Of Morphine Research Articles

A Single Dose of Intrathecal Morphine Without Local Anesthetic Provides Long-Lasting Postoperative Analgesia After Radical Prostatectomy and Nephrectomy

PurposePain after open urological procedures is often intense. The aim of the study was to compare the efficacy of intrathecal morphine with systemic analgesia approaches. DesignProspective, randomized, single-blind controlled study. MethodsPatients undergoing open prostatectomy or nephrectomy were randomly divided into the intervention group or the control group. Patients in the intervention group received morphine 250 mcg in 2.5 mL saline intrathecally. Anesthesia was identical in both groups. All patients were admitted to the intensive care unit (ICU) postoperative and received paracetamol 1 g intravenously every 6 hours and diclofenac 75 mg intramuscularly every 12 hours. If postoperative pain exceeded four on the numeric rating scale, morphine 10 mg was administered subcutaneously. Pain intensity, time to first dose of morphine, morphine doses, and side effects were recorded. FindingsIn total, 41 patients were assigned to the intervention group and 57 to the control group. The time to administration of the first dose of morphine was significantly (P < .001) longer in the intervention group when compared to controls. This observation was also noted individually for patients undergoing nephrectomy (36.86 hours vs 4.06 hours) and prostatectomy (33.13 hours vs 4.5 hours). Many patients did not need opioids after surgery in the intervention group (nephrectomy 72% vs 3%, prostatectomy 75% vs 4.5%, P < .001). There was no significant difference in the incidence of side effects. ConclusionsThe results of our study confirmed that preoperative intrathecal morphine provides long-lasting analgesia and reduces the need for postoperative systemic administration of opioids. Adverse effects are minor and comparable between groups.

Three ultrasound guided plane blocks for perioperative analgesia in patients undergoing radical cystectomy: a randomized clinical trial

Background &amp;objective: Transmuscular quadratus lumborum plane block (QLPB), paravertebral plane block (PVPB), and erector spinae plane block (ESPB) are three regional anesthesia techniques for management of perioperative pain for surgical procedures on the trunk, including thorax and abdomen. We compared the effectiveness of PVPB, QLPB type III (QL3), and ESPB for perioperative analgesia during radical cystectomy performed for bladder cancer.&#x0D; Methodology: This randomized double-blind trial was performed on 120 patients, aged above 18 years, undergoing radical cystectomy under general anesthesia. Individuals were randomly divided into 3 equal groups: ESPB, PVPB, and QLPB. Blocks were performed under ultrasound guidance preoperatively on each side with 30 ml of 0.25% bupivacaine. Time to perform block and time to the first dose of morphine postoperatively, were noted. Intra-operative hemodynamic data, including MAP and heart rate (HR) were noted every 10 min for an hour, and then at 30 min intervals. Postoperatively, MAP and HR were recorded at 0, 2, 6, 12 and 24 hours. The connection between qualitative factors was investigated using the chi-square test and Fisher's exact test. For the purpose of comparing the groups, one-way ANOVA and the Bonferroni correction were used. A two-tailed P value &lt; 0.05 was considered significant.&#x0D; Results: Time to perform block was substantially reduced in ESPB and QL3 groups compared to PVPB group. Time to the first dose of morphine was substantially delayed in the PVPB group than ESPB and QL3 groups. Total 24 h morphine consumption was substantially lower in the PVPB group than ESPB and QL3 groups. Postoperative visual analog scale measurements were substantially lower at 15 min, 30 min, and 12 h in the PVPB group than ESPB and QL3 groups and at 6 h in the ESPB and QL3 groups than in PVPB group. Postoperative mean arterial blood pressure and heart rate measurements were substantially reduced at 0 and 12 h in the PVPB group than in ESPB and QL3 groups and at 6 h in the ESPB and QL3 groups than in PVPB group.&#x0D; Conclusions: The ultrasound guided paravertebral plane block was superior to quadratus lumborum plane block type III and erector spinae plane block in providing more effective analgesia but with higher time to perform block.&#x0D; Abbreviations: ESPB- Erector Spinae Plane Block; PVPB- Paravertebral Plane Block; QLPB- Quadratus Lumborum Plane Block; QL3- Quadratus Lumborum Plane Block Type III&#x0D; Keywords: Paravertebral Plane Block; Quadratus Lumborum Plane Block; Erector Spinae Plane Block; Ultrasound; Radical Cystectomy&#x0D; Citation: Seif NE, El-Kholy MM, Ali AR, Zalat MM, Elshazly M. Three ultrasound guided plane blocks for perioperative analgesia in patients undergoing radical cystectomy: a randomized clinical trial. Anaesth. pain intensive care 2024;28(1):85-91; DOI: 10.35975/apic.v28i1.2381&#x0D; Received: September 28, 2023; Reviewed: October 31, 2023; Accepted: October 31, 2023

Ultrasound-Guided Bilateral Erector Spinae Plane Block vs. Ultrasound-Guided Bilateral Posterior Quadratus Lumborum Block for Postoperative Analgesia after Caesarean Section: An Observational Closed Mixed Cohort Study.

ESP block (ESPB) and posterior Quadratus Lumborum Block (pQLB) have been proposed as opioid-sparing techniques for the management of pain after abdominal surgery. Between December 2021 and October 2022, we conducted a retrospective comparative study at the delivery suite of Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, to compare the efficacy of ESPB and pQLB in preventing postoperative pain after an elective caesarean section (CS). The primary outcome was total morphine consumption in the first 24 h. Secondary outcomes were time to first opioid request; Numerical Pain Rating Scale (NPRS) at 0, 2, 6, 12 and 24 h; vital signs; adverse events. Fifty-two women were included. The total cumulative dose of morphine was not significantly different between the two groups of patients (p = 0.897). Time to first dose of morphine, NPRS values and haemodynamic parameters were not statistically different between the two groups. NPRS values significantly increased (p < 0.001) at the different time intervals considered. The need for rescue doses of morphine was lower in the ESPB group compared to the pQLB group (hazard ratio of 0.51, 95% CI (0.27 to 0.95), p = 0.030). No adverse event was reported. ESPB seems to be as effective as pQLB in providing analgesia after CS.

Comparison of postoperative IL-6 and IL-10 levels following Erector Spinae Plane Block (ESPB) and classical Thoracolumbar Interfascial Plane (TLIP) block in a posterior lumbar decompression and stabilization procedure: a randomized controlled trial

Background and objectivesThe erector spinae plane block (ESPB) and classical thoracolumbar interfascial plane (TLIP) block can reduce postoperative pain in lumbar surgery. In this study, we compared the efficacy of ESPB and classical TLIP block in providing perioperative analgesia in patients undergoing lumbar posterior decompression and stabilization by comparing postoperative pain, opioid consumption, and IL-6 and IL-10 serum concentrations between ESPB and classical TLIP block.MethodThis was a prospective, double-blinded, randomized controlled trial in tertiary referral hospitals. Forty patients were randomized into two equal groups, each receiving either ESPB or classical TLIP block. The primary outcome was the difference in IL-6 and IL-10 serum concentrations at baseline and 6 h after lumbar posterior decompression and stabilization. The secondary outcome was total opioid consumption and pain score 24 h post-operatively.ResultThere were no significant differences between the ESPB and classical TLIP block groups in pain score, IL-6 and IL-10 concentration change, and total opioid consumption post-operatively. There was a significant difference in the time until the first dose of morphine was needed between the ESPB and classical TLIP block groups (300 min vs. 547.5 min; p = 0.002).ConclusionESPB and classical TLIP block performance during lumbar surgery have comparable pain scores, IL-6 and IL-10 concentration differences pre- and post-operation, and total opioid consumption post-operatively. However, classical TLIP block provides a prolonged duration of analgesia.Trial registrationClinicalTrials.gov NCT04951024.

Outcomes in Vaso-Occlusive Crisis Treatment in the Emergency Department Vs. Acute Care Observation Center

I NTRODUCTION: Acute painful vaso-occlusive crises (VOC) are the leading cause of emergency department (ED) encounters and hospital admissions for those with sickle cell disease (SCD). For SCD patients, the goal of the sickle cell acute care observation unit (ACOU) at University of Illinois Health (UIH) is to improve patient outcomes by providing immediate care for an uncomplicated VOC. At our urban hospital which cares for more than 500 adult SCD patients, a considerable portion of SCD patients, despite having access to the ACOU, continue to present to the ED for treatment of an uncomplicated VOC. In order to help improve our current system, this study investigated outcomes in SCD patients who receive care for an uncomplicated VOC in the ACOU versus the ED at UIH. METHODS: By querying the electronic medical record, a retrospective study was conducted to analyze outcomes of encounters from the ACOU and ED at UIH between October 2019 and December 2019, specifically including SCD patients ≥18 years old who received morphine for treatment of an uncomplicated VOC. Encounters for complicated VOCs such as acute chest syndrome and stroke were excluded. Endpoints collected include time to first dose of morphine, total milligrams (mg) of IV morphine equivalents given, number of total morphine doses, admission rates, subsequent hospital length of stay, and 30-day inpatient admission rates. Time to the first dose (log transformed) and total dose in mg were analyzed by linear mixed effects models. The number of doses and hospitalization days were analyzed by negative binomial mixed effects model. Admissions and 30-day admissions were analyzed by logistic mixed effects models. These models adjusted for age, gender, and severe Hb genotype (HbSS or HbS beta0-thalassemia) and treated patient identity as random effect. P values were obtained from Wald- test. RESULTS: The ACOU data set contains 394 patient encounters for 79 patients with a median age of 33 years (interquartile range [IQR], 28-40), 71% female, and 73% with severe sickle genotypes. The ED data set contains 391 patient encounters for 128 patients with a median age of 30 years (IQR, 26-41), 53% female, and 74% with severe sickle genotypes. In the ACOU, the median time to first dose of morphine was 49 minutes (IQR, 39-60) compared to 107 minutes (IQR, 71-194) in the ED. The time to first dose was significantly longer in the ED compared to the ACOU (eβ=2.5, p &amp;lt;2×10-16). There was no significant difference in the total number of morphine doses received nor the total mg of morphine received between the two locations. Admission rate from ACOU was 6.6% compared to 53% from ED (OR=0.019, p=2x10-16). Of those admitted, the median number of hospitalization days from the ACOU was 4 days (IQR, 2.3-5.8) and 4 days (IQR, 2.0-6.5) from the ED. There was no significant difference in hospitalization days (p=0.6). The 30-day admission rate was 55% from the ACOU compared to 58% from the ED. 30-day admission rate however had strong intra-patient correlation (i.e., a patient was likely re-admitted multiple times): 44% of patients from the ACOU had admissions within 30 days of their ACOU visit compared to 32% from the ED. Controlling for the intra-patient correlation, ACOU visits had a higher 30-day admission rate than ED visit (OR=2.8, p=0.0015). DISCUSSION: SCD patients treated for an uncomplicated VOC at the sickle ACOU at UIH had a significantly shorter time to initial dose of IV pain medication. The wait time in the ED before first dose of IV pain medication received was more than double than those treated in the ACOU. Patients treated for an uncomplicated VOC in ACOU and ED had similar hospitalization days without a statistically significant difference. The 30-day admission rate to the inpatient setting was comparable for those treated in the ED versus the ACOU. However, given that only 6.6% of patients from the ACOU were admitted during the study period, this suggests that most patients who use both the ED and ACOU tend to be subsequently admitted from the ED. SCD patients may be presenting to the ED for treatment of VOC if capacity in the ACOU is exceeded or are presenting outside of hours of operation (currently 2 shifts Monday through Saturday). Therefore, improving access to our ACOU by increasing capacity and hours of operation may subsequently also lead to a decrease in time to first dose of medication and decrease in the overall 30-day admission rate. Disclosures Gordeuk: Imara: Research Funding; CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding.

Intraoperative Ketamine and Magnesium Therapy to Control Postoperative Pain After Abdominoplasty and/or Liposuction: A Clinical Randomized Trial.

PurposeThis study aimed to compare the effects of ketamine and ketamine associated with magnesium on opioid consumption and pain scores in patients undergoing abdominoplasty and/or liposuction compared to standard treatment.Patients and MethodsA total of 63 patients were included and randomized as follows: 21 patients in the Control group, 20 patients in the Ketamine group (Ket), and 22 patients in the Ketamine-magnesium group (KetMag). The KetMag group received an IV bolus of 0.3 mg/kg of ketamine and 50 mg/kg magnesium, followed by continuous infusion of ketamine (0.15 mg/kg/h) and magnesium (10 mg/kg/h) until extubation. The Ket group received the same bolus and infusion of ketamine, together with a bolus and continuous infusion of placebo instead of magnesium. The Control group received saline instead of ketamine and magnesium. The groups were compared in morphine consumption during the first 12h, body-postoperative pain and disability scale until the 90th day, the time until the first morphine request on the PCA pump, pain scores, and the adverse effects related to the use of study drugs.ResultsThe KetMag group had a lower morphine consumption by almost 50% during the first 12h than the Control and the Ket groups. In addition, the KetMag group required the first dose of morphine later than the other two groups. There were no differences in the adverse effects of the proposed treatments. Finally, multiple linear regression and a nonlinear approach analysis indicated that the Control group experienced a higher degree of pain and increased morphine consumption per hour than Ket and KetMag groups.ConclusionCo-administration of intraoperative ketamine plus magnesium and ketamine alone are an effective and easy regime for reducing pain and opioid consumption in the postoperative period.

Comparative randomized study of continuous serratus anterior plane block versus continuous paravertebral block in post-mastectomy pain

BackgroundMany analgesic methods have been used to control post-mastectomy pain. Both thoracic paravertebral and serratus anterior blocks are recent regional techniques with promising results. The aim of this study was to compare safety and analgesic efficacy of both techniques in controlling post-mastectomy pain.MethodsThe study was conducted from January 1, 2019, till January 10, 2019, on 60 female patients ASA class ≤ 2 undergoing modified radical mastectomy. After induction of balanced general anesthesia patients received either continuous thoracic paravertebral block (group P) or continuous serratus anterior block (group S). Twenty milliliters of levobupivacaine 0.25% were injected in each technique under ultrasound guidance followed by continuous infusion of 5 ml/h levobupivacaine 0.125% through a 22-gage catheter. IV morphine was given postoperatively by patient-controlled analgesia. In both groups, we measured time to first dose morphine, total 24 and 48 h morphine consumption, vital signs, visual analog scale, and side effects of each technique.ResultsThe demographic data (age, body mass index, and duration of surgery) were comparable in both groups. The time for first dose of morphine was significantly longer in group P (368 ± 36 min) than group S (270 ± 37.65 min) with P value < 0.001. Total morphine consumption in milligram at both 24 and 48 h were significantly less in group P (8.1 ± 0.8, and 11.5 ± 1 respectively) than in group S (10.1 ± 1.3 and 14.2 ± 1.4), with limited side effects in both groups.ConclusionBoth continuous paravertebral and serratus anterior plane blocks are safe good alternatives to control post-mastectomy pain. However continuous paravertebral block provides better analgesic profile.

Evaluation of the effectiveness of the Quadratus Lumborum Block type I using ropivacaine in postoperative analgesia after a cesarean section - a controlled clinical study.

Quadratus Lumborum Block in contrast to Transversus Abdominis Plane Block contains a unique component which not only stops somatic pain but also inhibits visceral pain by spreading the local anesthetic to the paravertebral space. This study was designed to determine whether performing the Quadratus Lumborum Block type I in patients un-dergoing cesarean section would be associated with both decreased morphine consumption and decreased pain levels in the postoperative 48-hour period. Sixty patients undergoing caesarean section under spinal anesthesia were randomly and equally assigned to one or other of two groups: QLB I (who received Bilateral Quadratus Lumborum Block type I with the use of 24 mL 0.375% ropivacaine per side) or a Control group. In both groups, on-demand morphine analgesia was administered postoperatively within the first 48 hours. The following were measured: the morphine consumption; the time elapsed from the C-section until the first dose of morphine; and the levels of pain intensity among patients in rest (numeral pain rating scale). There were no statistically significant demographic data differences between the QLB I and Control groups. The following significant differences were observed in the 48-hour postoperative period: morphine consumption was higher in the Control group (p = 0.000); the time elapsed from the C-section until the first dose of morphine was longer in QLB I group (p < 0.05); and the median of the pain numeric rating scale was higher in the Control group (p < 0.05). Quadratus Lumborum Block type I significantly reduces morphine consumption and pain levels up to 48 hours postoperatively.

Treatment of the acute sickle cell vaso‐occlusive crisis in the Emergency Department: a Brazilian method of switching from intravenous to oral morphine

Describe the treatment of patients with vaso-occlusive crises (VOC) in a Brazilian emergency department (ED) and the successful switch from intravenous to oral morphine. We analyzed records of 315 patients with sickle cell disease using two different protocols for pain: one in March 2010 prescribing intravenous morphine every 4 h throughout their stay, and another in March 2011 and 2012 prescribing one initial dose of intravenous morphine followed by equianalgesic doses of oral morphine every 4 h. Patients were triaged into three groups: mild, moderate, and severe VOC. The mild group was treated within 1 h after triage, the moderate within 30 min and the severe was treated immediately. Patients whose pain was not relieved within 6 h after the first dose of morphine were transferred into a different holding area of the ED where they continued to receive the same treatment for 48 h after which they were hospitalized if still in pain. The number of patients who stayed <24 h in the ED increased significantly from 63 in 2010 to 87 in 2012, and the number of admissions decreased from 26 in 2010 to 10 in 2012. The incidence of acute chest syndrome decreased from 8.5% in 2010 to 1.9% in 2012. Patients treated with oral morphine stayed a shorter time in the ED, had more pain relief, were admitted less frequently, and had less acute chest syndrome. These differences may be due to environmental, cultural, psychological, and pharmacogenetic factors.

Assessment of the Effect of Ketamine in Combination with Remifentanil on Postoperative Pain

Background and objectives: The combination of ketamine and remifentanil seems to be associated with better analgesia and duration. The aim of this study was to evaluate whether a ketamine- remifentanil combination promotes improved postoperative analgesia. MethodsProspective, randomized, double blind study of 40 patients undergoing video laparoscopic cholecystectomy. Anesthesia was performed with remifentanil, propofol, atracurium, and 50% oxygen. Group 1 (GI) patients received remifentanil (0.4 mcg.kg-1.min-1) and ketamine (5 mcg.kg-1.min-1) and Group 2 (G2) received remifentanil (0.4 mcg.kg-1.min-1) and saline solution. Morphine 0.1 mg.kg-1 was administered at the end of the procedure, and postoperative pain was treated with morphine via PCA. We evaluated the severity of postoperative pain by a numerical scale from zero to 10 during 24 hours. We registered the time to the first analgesic supplementation, amount of morphine used in the first 24 hours, and adverse effects. ResultsThere was a decrease in pain severity between extubation and other times evaluated in G1 and G2. There was no significant difference in pain intensity between the groups. There was no difference between G1 (22 ± 24.9 min) and G2 (21.5 ± 28.1 min) regarding time to first dose of morphine and dose supplement of morphine consumed in G1 (29 ± 18.4 mg) and G2 (25.1 ± 13.3 mg). ConclusionThe combination of ketamine (5 mcg.kg-1.min-1) and remifentanil (0.4 mcg.kg-1.min-1) for cholecystectomy did not alter the severity of postoperative pain, time to first analgesic supplementation or dose of morphine in 24 hours.

Assessment of the Effect of Ketamine in Combination with Remifentanil on Postoperative Pain

Background and objectivesThe combination of ketamine and remifentanil seems to be associated with better analgesia and duration. The aim of this study was to evaluate whether a ketamineremifentanil combination promotes improved postoperative analgesia. MethodsProspective, randomized, double blind study of 40 patients undergoing video laparoscopic cholecystectomy. Anesthesia was performed with remifentanil, propofol, atracurium, and 50% oxygen. Group 1 (GI) patients received remifentanil (0.4mcg.kg-1.min-1) and ketamine (5mcg.kg-1.min-1) and Group 2 (G2) received remifentanil (0.4mcg.kg-1.min-1) and saline solution. Morphine 0.1mg.kg-1 was administered at the end of the procedure, and postoperative pain was treated with morphine via PCA. We evaluated the severity of postoperative pain by a numerical scale from zero to 10 during 24hours. We registered the time to the first analgesic supplementation, amount of morphine used in the first 24hours, and adverse effects. ResultsThere was a decrease in pain severity between extubation and other times evaluated in G1 and G2. There was no signifi cant difference in pain intensity between the groups. There was no difference between G1 (22±24.9min) and G2 (21.5±28.1min) regarding time to first dose of morphine and dose supplement of morphine consumed in G1 (29±18.4mg) and G2 (25.1±13.3mg). ConclusionThe combination of ketamine (5mcg.kg-1.min-1) and remifentanil (0.4mcg.kg-1.min-1) for cholecystectomy did not alter the severity of postoperative pain, time to first analgesic supplementation or dose of morphine in 24hours.

Patient Weight as a Predictor of Pain Response to Morphine in the Emergency Department

Study Objectives: There is little evidence that patient weight is associated with pain response to morphine in the emergency department (ED). The primary outcome of this study is to identify demographic variables including patient weight that are associated with an adequate pain reduction after the first dose of morphine. Methods: A retrospective chart review of all patients with severe nontraumatic abdominal pain receiving intravenous morphine was conducted in our ED over a 3-month time period. Pain score, using an 11-point verbal numerical pain scale (0-10), was measured before and after each dose of morphine. Adequate response was defined as a ≥ 4-point reduction from baseline pain score. Results: A total of 105 patients were included in the analysis. Univariate logistic regression analyses stratified by dose (2 or 4 mg) showed that patient weight was not predictive of adequate pain response after the first dose of morphine (2 mg: odds ratio = 1; 95% confidence interval 0.97-1.03; P = .88; 4 mg: odds ratio = 1; 95% confidence interval 0.97-1.03; P = .86). Conclusions: Patient weight may not predict pain response to morphine in the ED. Dosing strategies based on patient weight may not be necessary in this patient population.

Somatic paravertebral block decreases opioid requirements in children undergoing appendectomy

Somatic paravertebral block (SPVB) appears to provide effective and prolonged nerve block in children; however, study of its use in this population is limited. We compared SPVB with no block in children undergoing appendectomy. Thirty-six children aged 3-16 yr undergoing open appendectomy were involved in this prospective randomized controlled study. Anesthesia was induced with propofol and maintained with isoflurane in N(2)O/oxygen. All subjects received fentanyl, acetaminophen and ketorolac during anesthesia. Group I (SPVB) subjects received a right SPVB at T(11), T(12), and L(1) using 0.2% ropivacaine 0.25 mL.kg(-1) with epinephrine 1:200,000 preoperatively. Group II (Control) had only bandaids applied to skin. Both groups were given morphine 0.05 mg.kg(-1) iv every 2 hr if pain scores reached 5/10 on a visual analogue scale. Acetaminophen was administered postoperatively every 6 hr to both groups. Time to first dose of morphine, total dose of morphine in 24 hr, and any adverse effects up to 24 hr after surgery were recorded. Group I (SPVB) subjects required significantly less morphine than Group II (Control) patients (0.12 +/- 0.07 vs 0.34 +/- 0.15 mg.kg(-1), respectively; P < 0.001), and time to their first dose was significantly longer (7.1 +/- 4.4 vs 2.5 +/- 1.6 hr, respectively; P < 0.001). Incidence of vomiting was 11% with Group I and 27% with Group II (P = 0.21). No other adverse effects were observed in either group. In children undergoing appendectomy, SPVB provides better pain relief than no block and reduces opioid requirements. Side effects were not statistically different between groups.

Postoperative Analgesia for the Surgical Correction of Congenital Clubfoot. Comparison between Peripheral Nerve Block and Caudal Epidural Block

Correction of congenital clubfoot (CCF) is associated with severe postoperative pain. Caudal epidural block associated with general anesthesia is the anesthetic technique used more often in children, but it is limited by the short duration of the postoperative analgesia. Peripheral nerve blocks are associated with a low incidence of complications and prolonged analgesia. The objective of this study was to compare the duration of analgesia in peripheral nerve blocks and caudal block, as well as morphine consumption in the first 24 hours after correction of CCF in children. This is a randomized, double-blind study with children undergoing surgeries for posteromedial release of CCF, who were divided in four groups according to the anesthetic technique: caudal (ACa), sciatic and femoral block (IF), sciatic and saphenous block (IS), and sciatic block and local anesthesia (IL), associated with general anesthesia. In the first 24 hours, patients received oral dypirone and acetaminophen, and they were evaluated by anesthesiologists who were unaware of the technique used. Oral morphine (0.19 mg x kg(1) per day) was administered according to the scores of the CHIPPS (Children's and infants' postoperative pain scale) scale. One hundred and eighteen children separated into four groups: ACa (30), IF (32), IS (28), and IL (28) participated in this study. The mean time between the blockade and the first dose of morphine was 6.16 hours in group ACa, 7.05 hours in group IF, 7.58 in IS, and 8.18 hours in IL. Morphine consumption was 0.3 mg.kg-1 per day in all four groups. Significant differences were not observed among the groups. peripheral nerve blocks did not promote longer lasting analgesia or a decrease in morphine consumption in the first 24 hours in children undergoing CCF correction when compared to caudal epidural block.

Graphical Display of Data Could Reveal Errors in Statistical Tests

Hôpital Ambroise Paré, Boulogne Billancourt, France. bruno.guignard@apr.aphp.frI read with interest the article about intraoperative remifentanil infusion by Lee et al. I have major concerns regarding the nonsignificance of chi-square tests for the behavioral pain score during the first 15 min in the recovery room. The bar representation in their figure 1 is appropriate for expressing these results and clearly shows a different comportment of patients in the two groups. After redoing the analysis by extrapolated number of patients according to bar height, it seems that, as expected, significant activity for chi-square tests is very high at all times studied (). Calculations were made with JMP 5.1 (SAS Institute, Cary, NC). The comment in the text says that 60% of patients in the remifentanil group versus 40% in the nitrous oxide group have a behavioral pain score of 0. That does not match the figure in the article. Furthermore, the percentage of total patients exceeds 100% at T5 for the remifentanil group.If these results are not type errors, we could have question about the morphine titration. In our study, the morphine titration was based essentially on behavioral scale during the first 15 min after extubation, because of the difficulty to have correct pain assessment just based only on the visual analog pain scale score at this moment. Another difference with our study is the use of fentanyl at induction and morphine at skin incision. The time to first dose of morphine does not appear in the results. The authors' conclusion could be right, but the discrepancies in the presented data may alter this finding. Opioid tolerance is not always clinically significant because of patient variability, surgery duration, opioid dosage, or concomitant medication. Graphics can help us to show clinical evidence, and statistical tests are used to confirm and valid ideas revealed by data. The high publication pressure should not deserve statistical review. Analysis and criticism are the guaranties of medical research.Hôpital Ambroise Paré, Boulogne Billancourt, France. bruno.guignard@apr.aphp.fr

RGS-Rz and RGS9-2 proteins control mu-opioid receptor desensitisation in CNS: the role of activated Gαz subunits

Two consecutive icv administrations of analgesic doses of mu-opioid receptor agonists lead to a profound desensitisation of the latter receptors; a third dose produced less than 20% of the effect obtained with the first administration. Desensitisation was still effective 24 h later. Impairing the activity of Gαz but not Gαi2 subunits prevented tolerance developing after the administration of three consecutive doses of morphine. Further, the icv injection of Gαi2 subunits potentiated morphine analgesia and abolished acute tolerance, whereas icv-administered Gαz subunits produced a rapid and robust loss of the response to morphine. The RGSZ1 and RGSZ2 proteins selectively deactivate GαzGTP subunits, and their knockdown increased the effects produced by the first dose of morphine. However, impairing their activity also accelerated tachyphylaxis following successive doses of morphine, and facilitated the development of acute morphine tolerance. In contrast, inhibiting the RGS9-2 proteins, which bind to GαoGTP and GαiGTP but only weakly deactivates them, preserved the effects of consecutive morphine doses and abolished the generation of acute tolerance. Therefore, desensitisation of mu-opioid receptors can be achieved by reducing the responsiveness of post-receptor elements (via the possible action of activated Gαz subunits) and/or by depleting the pool of receptor-regulated G proteins that agonists need to propagate their effects, e.g., through the activity of RGS9-2 proteins.

Experimental study of the morphine de-addiction properties of Delphinium denudatum Wall.

BackgroundOur aim was to explore the de-addiction properties of Delphinium denudatum Wall. in morphine dependent rats.MethodsCharles Foster male albino rats were made morphine dependent by injecting morphine sulphate in increasing doses twice a day for 7 days. The spontaneous withdrawal signs observed 12 h after the last dose were quantified by the 'counted' and 'checked' signs. The drug (alcoholic extract of Delphinium denudatum) was administered p.o. in different regimen: a) single dose (700 mg/kg) 10 h before the first dose of morphine, b) single dose (700 mg/kg) 10 h after the last dose of morphine, c) multiple doses (350 mg/kg) along with morphine twice a day for 7 days.ResultAdministration of Delphinium denudatum extract caused significant reduction in the frequency of counted signs as well as the presence of checked signs of morphine withdrawal. The maximum reduction was observed in regimen 'b' followed by regimen 'c' and 'a'.ConclusionDelphinium denudatum Wall. significantly reduces the aggregate scores for all parameters in morphine withdrawal syndrome by central action and thus may prove to be an alternative remedy in morphine de-addiction.

P REHOSPITAL A DMINISTRATION OF M ORPHINE FOR I SOLATED E XTREMITY I NJURIES : A C HANGE IN P ROTOCOL R EDUCES T IME TO M EDICATION

Objective. To evaluate the effect of a new protocol allowing paramedics to administer morphine without a physician order to patients with extremity trauma with respect to time of morphine administration, scene time, morphine amount and number of doses per patient, and proportion of patients receiving morphine. Methods. Data were abstracted from transport forms for a ten-month period prior to the implementation of the new protocol and for nine months after implementation. Data elements included patient age and sex, date, time of EMS arrival on scene, amount and number of morphine doses, and total number of patients transported. Results. Implementation of the new protocol was associated with a decrease in time between emergency medical services (EMS) arrival on scene and administration of the first dose of morphine from 18.8 to 16.7 minutes, a difference of 2.1 minutes [95% confidence interval (95%CI) 1.3, 2.9]. The proportion of patients receiving analgesia at the scene, rather than during transport, increased from 62.7% before the protocol change to 69.5% after, an increase of 6.8% (95% CI 2.7, 11.0). Transports before and after implementation of the new protocol did not differ with respect to patient sex, age, or chief complaint; number of morphine doses or total morphine administered per patient; or proportion of prehospital patients receiving morphine. Conclusions. A change in protocol that permits trained paramedics to administer morphine without physician approval reduces time to analgesia administration without influencing the amount of morphine delivered per patient or the rate of prehospital morphine use. Further study should measure the effect on base hospital physician interruptions and patient outcome.

Effects of morphone on choline acetyltransferase levels in the caudate nucleus of the rat.

1. Choline acetyltransferase (choline-o-acetyltransferase 2.3.1.6.) concentrations were determined in the caudate nucleus, thalamus, and cortex of control and morphine treated rats. The enzyme was assayed using a modified radiochemical method on a number of selected days, one hour after the last injection of 30 mg/kg of morphine and also during the subsequent phase of abstinence from morphine.2. Significant lowering of choline acetyltransferase activity in the caudate nucleus area was found in two cases, one hour after the first dose of morphine and upon subsequent abstinence from morphine.3. The enzyme activity in the two other parts of the brain remained at the normal levels.4. The presence of endogenous inhibitors formed during morphine administration was excluded.5. The relationship of a possible effect of morphine on the tissue binding of the enzyme and the subsequent lowering of its activity was tested by homogenization of the caudate nucleus area in different media. The decrease in enzyme activity occurred in all extraction media one hour after morphine administration.6. Inhibitory effects of in vitro addition of morphine to caudate nucleus homogenate, obtained from normal and morphine treated rats, were found to occur only at very high concentrations of the drug, negating the possibility of direct inhibitory effects of morphine.7. These experiments suggest two possible causes of the observed effects, which can be responsible for the lowering of enzyme activity, and can be operative simultaneously: (1) a negative feedback mechanism of accumulated acetylcholine, occurring after the first dose of morphine, and (2) the possible changes in enzyme configuration produced by morphine treatment.