Severity Of Respiratory Depression Research Articles

Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction.

Globally, more than 100 000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time-points during his long-term diamorphine maintenance treatment. A single-subject study over 5years during which participant underwent experimental studies on diamorphine-induced respiratory depression, at changing maintenance doses. A clinical research facility. Participant Male subject on long-term injectable diamorphine (pharmaceutical heroin) maintenance treatment for heroin addiction. Physiological measures of oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ) and respiratory rate (RR) were used to indicate severity of respiratory depression. (1) After diamorphine injection, respiratory regulation became abnormal, with prolonged apnoea exceeding 20sec (maximum 56sec), elevated ETCO2 (maximum 6.9%) and hypoxaemia (minimum SpO2 80%). (2) Abnormalities were greater with highest diamorphine dose: average SpO2 was 89.3% after 100mg diamorphine versus 93.6% and 92.8% for the two 30-mg doses. (3) However, long apnoeic pauses and high levels of ETCO2 % were also present after lower doses. With marked inter-session variability, these findings corroborate observations of inconsistent relationships between opioid dose and overdose risk.

Comparison of Post Cesarean Analgesia with Epidural BupivacaineFentanyl v/s Bupivacaine-Nalbuphine v/s Bupivacaine-Butorphanol – A Double Blinded Randomized Study

OBJECTIVE: Comparison and study of post cesarean analgesia and side effect profile of epidural 0.125% bupivacaine-fentanyl v/s 0.125% bupivacaine-nalbuphine v/s 0.125% bupivacaine – butorphanol. DESIGN: Randomized, double-blinded study. 80 ASA physical status I and II women, aged 20-30 years, undergoing Elective Cesarean Section. INTERVENTIONS: Patients were randomly allocated to four groups during the postoperative period to receive one of four epidural regimens: Group 1(NS): 10ml of 0.125% Bupivacaine + 1ml of Normal Saline; Group 2(FENT) 10ml of 0.125% Bupivacaine + 50ug of Fentanyl (1ml); Group 3(NALB) 10ml of 0.125% Bupivacaine + 5mg of Nalbuphine(0.5ml) +0.5ml of Normal saline to make it into 1ml; Group 4 (BUTOR): 10ml of 0.125% Bupivacaine + 1mg of Butorphanol (1ml). MEASUREMENTS: Onset and duration of analgesia were recorded. Hemodynamic variables, pain scores, sedation scores, and respiratory rate were monitored for 24 hours. Frequency and severity of respiratory depression, sedation, pruritus, nausea, and vomiting were recorded. RESULTS: The data of only 77 patients were included for calculation because 3 patients were dropped from the study as they had patchy sensory blockade to an extent of converting to GA. There was no statistically significant difference in demographic parameters. The mean onset of analgesia and times to reach peak analgesia were significantly shorter while the mean durations of analgesia were significantly longer in the groups receiving fentanyl, nalbuphine & butorphanol than in the group receiving bupivacaine alone. The onset of analgesia was earliest with Butorphanol group (3.42min) followed by fentanyl group(4.20min), Nalbuphine roup(5.42min) & finally by control group(8.22min). The duration of analgesia was maximum with Butorphanol group (mean of 360min), followed by Fentanyl group (mean of 280min), Nalbuphine group (mean of 245) & control group (mean of 211min). Satisfaction with the pain relief given was assessed by 1. Ability for independent side to side movement 2. VAS for satisfaction. It was observed that satisfaction was more with Butorphanol group followed by Nalbuphine group, Fentanyl group & by control group in the descending order. Sedation was observed in all the groups (Control – 17%, Fentanyl – 25%, Nalbuphine – 58%, Butorphanol – 63%. Butorphanol & Nalbuphine groups had more incidence of sedation & higher grades of sedation (Grade 4) Nausea & Vomiting was observed in both control group (incidence of 6%) & fentanyl group (incidence of 20%) Pruritus was observed only in the fentanyl group with a incidence of 15%. None of the patients developed hypotension, Bradycardia, respiratory depression. CONCLUSIONS: Epidural 0.125% Bupivacaine combined with Butorphanol produces significantly earlier onset, longer duration and better quality of analgesia than 0.125% Bupivacaine - Nalbuphine combination / 0.125% Bupivacaine -Fentanyl combination / 0.125% Bupivacaine alone and is safe in parturients.

Commentary on: Use of Remifentanil and Alfentanil in Endotracheal Intubation: A Comparative Study.

Dear Editor, I read the paper by Imani et al. (1) with interest and must congratulate them in attempting to show the advantages of administering remifentanil for laryngoscopy and tracheal intubation in adult patients. It was interesting to know the experiences of colleagues with regard to tracheal intubation in noncardiac patients, as I use a combination of remifentanil and propofol in my daily practice in cardiac anesthesia. The primary goal of this study was to evaluate patients’ conditions during tracheal intubation after remifentanil compared with alfentanil. Although the scoring criteria were well defined, the question arises as to why the authors did not report the hemodynamic situation of the patients before and after induction of anesthesia, as other studies have done (2-5). Their report did not describe whether the patients had bradycardia or hypotension. We know that hemodynamic instability is a common feature of remifentanil, alfentanyl, and propofol, leading some researchers to use atropine as prophylaxis to overcome decreases in heart rate after induction with these drugs (2, 3). The other question is the time from injection to apnea or respiratory depression, if applicable. It would be helpful for colleagues to know this interval and the incidence of apnea in the remifentanil and alfentanil groups, as we already know that the incidence of apnea is high with opioids, especially in combination with other anesthetics, such as propofol. It is noteworthy that the rate and severity of respiratory depression with different dosages and combinations of anesthetic and analgesics are controversial (6). It appears from the study that there was no significant difference between the remifentanil and alfentanil groups scores regarding intubation condition rather than vocal cord patency score; however, the authors should clarify if there is any difference between genders and age groups.

Epidural butorphanol-bupivacaine analgesia for postoperative pain relief after abdominal hysterectomy

Study Objective To determine the efficacy of epidural butorphanol with and without bupivacaine in providing postoperative analgesia following abdominal hysterectomy. Design Randomized, double-blinded study. Settings Postoperative recovery area of a university-affiliated medical center. Patients 60 ASA physical status I and II women, aged 20-65 years, undergoing abdominal hysterectomy. Interventions Patients were randomly allocated to three groups during the postoperative period to receive one of three epidural regimens: two mg of butorphanol in 10 mL of normal saline (Group 1), two mg of butorphanol in 10 mL of 0.125% bupivacaine (Group 2), or two mg of butorphanol in 10 mL of 0.25% bupivacaine (Group 3). Measurements Onset and duration of analgesia were recorded. Hemodynamic variables, pain scores, sedation scores, and respiratory rate were monitored for 24 hours. Frequency and severity of respiratory depression, sedation, pruritus, nausea, and vomiting were recorded. Main Results The addition of butorphanol to bupivacaine resulted in significantly ( P < 0.05) faster onset of pain relief. The duration of analgesia was prolonged in patients receiving butorphanol with bupivacaine combination (8.68 ± 0.82 hrs, 9.82 ± 0.54 hrs) as compared with butorphanol alone (4.35 ± 0.66 hrs; P < 0.05). The differences between Groups 2 and 3 were not significant. Conclusions Addition of two mg of butorphanol to 0.125% of epidural bupivacaine resulted in rapid onset and longer duration of analgesia than did butorphanol alone.

Dosage trials with transmucosal carfentanil citrate in non-human primates

The traditional method of immobilizing non-human primates involves remote-delivery injection of anesthetic agents. Orally delivered, transmucosally absorbed opioids have been shown to be a non-stressful alternative method of pre-anesthetic drug administration in children and adults [Stanley et al., 1989]. This report describes several cases using transmucosal carfentanil in non-human primates to determine whether orally delivered carfentanil can be a safe, less stressful, and reversible method of sedation in these species. Regimen 1: Transmucosal carfentanil alone. Three chimpanzees (Pan troglodytes), two capuchin monkeys (Cebus apella), and two gibbons (Hylobates lar) were given carfentanil citrate as their sole pre-medication agent. Doses ranged from 2.0 to 4.0 μg/kg. After a median time of 22 minutes, all chimpanzees were nearly or completely immobilized and showed signs of severe respiratory depression. In contrast, the gibbons and capuchins showed moderate to profound sedation and no signs of respiratory depression. Regimen 2: Oral droperidol followed by transmucosal carfentanil. Four chimpanzees and two bonobos (Pan paniscus) were given a dose of 2.5 mg droperidol orally 45 minutes before transmucosal carfentanil administration. Two chimpanzees received 1.0 μg/kg carfentanil, and all other animals in this trial received a dose of 2.0 μg/kg. All individuals were nearly or completely immobilized with this protocol, and respiratory depression was much less severe. Regimen 3: Oral droperidol followed by transmucosal carfentanil for euthanasia. Two western lowland gorillas (Gorilla gorilla) were electively euthanized using oral droperidol followed by transmucosal carfentanil. Droperidol was administered as in Regimen 2, and doses of carfentanil were 14 μg/kg in the case of a developmentally disabled young gorilla, and 2 μg/kg for a severely debilitated geriatric gorilla with severe respiratory and cardiac disease. Respiratory arrest occurred at 12 and 10 minutes, respectively after carfentanil administration, with subsequent cardiac arrest. Transmucosal carfentanil appears promising as an anesthetic agent when administered alone to gibbons and capuchin monkeys, when administered in combination with droperidol to chimpanzees and bonobos, and when administered for purposes of elective euthanasia in gorillas. Administration of transmucosal carfentanil alone for immobilization of chimpanzees is not recommended because of the severity of respiratory depression observed. Zoo Biol 18:397–402, 1999. © 1999 Wiley-Liss, Inc.

Propofol and alfentanil for sedation during placement of retrobulbar block for cataract surgery

Study Objective: To determine if the addition of alfentanil to propofol is more effective than propofol alone to provide adequate conditions for placement of a retrobulbar block prior to cataract surgery. Design: Randomized, double-blinded study. Setting: Outpatients at a university hospital. Patients: 40 adult ASA physical status I, II, and III outpatients scheduled for elective cataract surgery. Interventions: Patients were randomly assigned to receive one of four drug combinations prior to the placement of a retrobulbar block: Group 1, propofol alone; Group 2, alfentanil 5 μg/kg plus propofol; Group 3, alfentanil 10 μg/kg plus propofol; Group 4, alfentanil 15 μg/kg plus propofol. All patients were preoxygenated by face mask for two minutes prior to drug administration. The quality of conditions for block placement were determined by: (1) assessing the amount of movement by the patients while the block needle was in place, (2) cooperativeness of the patients during the operation, (3) hemodynamic side effects, (4) incidence and severity of respiratory depression, (5) incidence of nausea and vomiting, (6) recall of placement of the block, and (7) time to discharge from the hospital. Measurements and Main Results: The addition of alfentanil to propofol for sedation prior to placement of the retrobulbar block resulted in a dose-dependent reduction in movement by the patients. However, the highest dose of alfentanil (15 μg/kg) resulted in the greatest frequency (40% of the patients in this group) of respiratory depression (SpO 2 < 90%). All patients were cooperative during the operation and responsive to verbal command within 5 minutes of placement of the block. In addition, all of the patients denied being nauseated, having vomited, or recalling block placement in the recovery room or the next day. Conclusions: The combination of alfentanil and propofol may be used to sedate patients in order to limit movement and provide a cooperative, alert patient with stable hemodynamics and limited respiratory depression during placement of retrobulbar block prior to ophthalmic surgery. However, excessive dosage of these drugs may result in hazardous respiratory depression in this patient population.