Rate Of Respiratory Depression Research Articles

Safety and efficacy of intrathecal morphine in early onset scoliosis surgery.

Intrathecal morphine (IM) is a popular adjunct for pain management in spinal deformity surgery for idiopathic scoliosis. It has not been studied in patients with early onset scoliosis (EOS). We retrospectively reviewed EOS patients undergoing growth-friendly surgery who received IM or did not receive IM (non-IM). Data from initial insertion and final fusion procedures were studied. IM was not used for lengthening procedures, short procedures (<3 h), patients with significant underlying respiratory issues, paraplegia, unsuccessful access and anesthesiologist discretion. We assessed pediatric ICU (PICU) admission and IM complications (respiratory depression, pruritus and nausea/vomiting), time to first postoperative opiate, and pain scores. There were 97 patients including 97 initial insertions (26 IM and 71 non-IM) and 74 patients with final fusions (17 IM and 57 non-IM). The first dose of opioids following insertion and final fusion occurred at 16.8 ± 3.8 and 16.8 ± 3.1 h postoperatively in the IM group compared to 5.5 ± 2.8 and 8.3 ± 3.2 h in the non-IM group, respectively ( P < 0.001). Postoperative pain scores were lower in the IM groups ( P = 0.001). Two patients with IM developed mild respiratory depression following initial insertion ( P = 0.01) but did not require PICU admission. The rate of respiratory depression was not different between the final fusion groups. There was no difference between pruritus and nausea/vomiting at the final fusion. Preincision IM can provide well-tolerated and effective initial postoperative analgesia in select children with EOS undergoing spinal deformity surgery.

Effect of additional equipotent fentanyl or sufentanil administration on recovery profiles during propofol-remifentanil\u2013based anaesthesia in patients undergoing gynaecologic laparoscopic surgery: a randomized clinical trial

BackgroundIn clinical practice, sufentanil has a stronger sedative effect on patients than fentanyl at equivalent doses. This study hypothesized that, at equivalent doses, patients undergoing gynaecologic laparoscopic surgery (GLS) receiving fentanyl would have an earlier emergence from anaesthesia (EA), a shorter time to extubation (TE), and a better degree of wakefulness. Therefore, this study evaluated the effects of equipotent doses of fentanyl and sufentanil on the quality of emergence in patients undergoing GLS. MethodsOne hundred seven patients scheduled for GLS under general anaesthesia were randomly divided into two groups and were induced with 0.35 µg/kg sufentanil (Group S; n = 55) or 3.5 µg/kg fentanyl (Group F; n = 52). When the GLS was almost over, the patient's abdominal cavity was flushed with warm saline, and 5 µg of sufentanil or 50 µg of fentanyl in a double-blind manner was intravenously injected into the patients. The primary outcomes of the study included EA, TE, the rate of leaving the surgical bed voluntarily and the incidence of endotracheal tube tolerance. The Ramsay Sedation Scale (RSS), and Verbal Rating Scale (VRS) scores at 15 and 30 min in the postanaesthesia care unit (PACU), as well as other adverse events, including nausea and vomiting, itching, delirium, dizziness, chills, and respiratory depression (SpO2 < 95%) in the PACU, were evaluated as secondary outcomes.ResultsThere were no statistically significant dissimilarities between the two groups with respect to baseline characteristics. For recovery, the EA (9.0 ± 4.8 min vs. 8.9 ± 3.0 min; P = 0. 146), TE (9.5 ± 4.7 min vs. 9.0 ± 3.0 min; P = 0.135), rate of leaving the surgical bed voluntarily (31.18% vs. 38.46%; P = 0.976), and incidence of endotracheal tube tolerance (94.55% vs. 96.15%; P = 0.694) were not significantly different between the two groups. In the PACU, the 15-min RSS score (2.07 ± 0.38 vs. 2.15 ± 0.36; P = 0.125), the 30-min RSS score (2.02 ± 0.13 vs. 2.04 ± 0.19; P = 0.207), the 15-min VRS score (0.50 ± 0.57 vs. 0.67 ± 0.55; P = 0.295), and the 30-min VRS score (0.45 ± 0.50 vs. 0.75 ± 0.52; P = 0.102) were not significantly different between Groups S and F. No adverse events, such as nausea, vomiting, pruritus, delirium, and tremors, occurred in either group. The rates of respiratory depression (1.82% vs. 1.92%; P = 0.968) and dizziness (0.00% vs. 4.85%; P = 0.142) were not different between Groups S and F in the PACU.ConclusionsThe majority of patients scheduled for GLS were able to rapidly and smoothly emerge from anaesthesia. After surgery, similar outcomes, including EA, TE, the incidence of endotracheal tube tolerance, the rate of leaving the surgical bed voluntarily, RSS scores, VRS scores, and adverse events in the PACU, were achieved for the patients between the two anaesthetic protocols.

Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis.

Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting. To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting. We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo®, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020. Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively. Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness. The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data. Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting. This study is registered as PROSPERO CRD42020201953. This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.

Evaluation of Monitored Anesthesia Care Involving Sedation and Axillary Nerve Block for Day-Case Hand Surgery.

Background: Ultrasound-guided axillary brachial plexus block (ABPB) is a technique of choice for regional anesthesia during hand and forearm surgery. Intravenous sedation may facilitate this procedure, particularly for those suffering from anxiety; however, it can also be associated with respiratory, cardiovascular, and neurological side effects. The objective of this study was to evaluate the effect of intravenous sedation on perioperative respiratory depression for patients undergoing day-case hand surgery under ABPB. Methods: A prospective, observational, single-center study was conducted between 1 May and 1 November 2016. Results: A total of 2318 patients were included, with 501 patients in the group with IV sedation and 1817 in the group without. A multivariable propensity-score matched analysis showed that the variables associated with the number of desaturation were: (i) sedation (aRR 1.534 [95% CI: 1.283 to 1.836]), (ii) age and sex, (iii) type of surgery, and iv) Body Mass Index (BMI). Conclusions: Supplementing ABPB with IV sedation was associated with an increased rate of respiratory depression (episodes of desaturation) compared to fully awakened patients. The rate of oxygen administration was also higher in sedated patients even though they had fewer cases of chronic respiratory diseases and fewer were active smokers than non-sedated patients. Future research should consider precisely evaluating patient satisfaction, as well as the differences between sedation and drug-free approaches.

Comparing Benzodiazepines-morphine-induced Respiratory Depression by Analyzing Respiratory Pattern in Rats

Background and Aim: Opioid and benzodiazepine family drugs are concurrently used in various patients. Considering the respiratory depressant effects of both classes, in this study, we investigated the effect of coadministration of morphine and several widely used benzodiazepines in the clinic on the rate of respiratory depression in rats. Methods &amp; Materials: Seventy adult male Wistar rats were randomly divided into 10 groups; morphine, midazolam, diazepam, lorazepam, alprazolam, morphine-midazolam, morphine-diazepam, morphine-lorazepam, and morphine-alprazolam. Respiration signal was recorded using whole-body plethysmography 15 minutes after the intraperitoneal injection of the drugs. The respiratory pattern was examined using several parameters; the mean value of inter-breath interval and the respiratory rate, as well as the coefficient of variation and sample entropy analysis of inter-breath interval. Ethical Considerations: This study was approved by the Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1397.327). Results: Analyzing respiratory data revealed that injecting the anxiolytic dose of alprazolam, and the combination of morphine-alprazolam and morphine-midazolam, altered the respiratory pattern. Such changes were associated with a decrease in the number of breaths and an increase in the inter-breath interval in the explored test animals, compared with the controls. The obtained data also indicated that morphine-midazolam injection increased the variability of the breathing pattern; such an alternation was associated with increased irregularity and decreased coefficient of variation of the inter-breath interval. Conclusion: The present research results suggested that the short-term injection of morphine-midazolam changes the respiratory pattern more severely than morphine combined with other benzodiazepines.

Respiratory depression following medications for opioid use disorder (MOUD)-approved buprenorphine product oral exposures; National Poison Database System 2003–2019

Background Medications for opioid use disorder (MOUD) including buprenorphine is recommended for patients with opioid use disorders. We sought to evaluate the frequencies of respiratory depression, intubation, and naloxone administration, and clinical outcomes among patients reported to the National Poison Database System (NPDS) following single-substance and multiple-substance buprenorphine oral exposures. Methods NPDS was queried for all MOUD-approved buprenorphine product exposures between 1 January 2003 and 31 December 2019. Data abstracted included year, route, gender, age, site of exposure, management site, medical outcome, recorded “related” respiratory depression (“respiratory rate <10 breaths/min and/or a SpO2 (pulse oximetry)≤90%), reported administration of naloxone and intubation in oral exposure cases followed to known outcome. Concomitant products were also recorded in multiple-substance buprenorphine cases. Results 27,275 (11,010 multiple and 16,265 single) buprenorphine oral exposures were identified and followed to known outcome. A 65-fold increase in reported cases was reported over the study interval. A steady increase in the frequency of more serious outcomes by year was also observed. Respiratory depression occurred at a frequency of 11.8% (pediatric single-substance), 11.2% (pediatric multiple-substance), 11.3% (adult single-substance), and 11.9% (adult multiple-substance). Among oral exposures of buprenorphine and only one other product, benzodiazepines, opioids, ethanol, and amphetamines were most common. Conclusions Oral exposures have increased substantially between 2003 and 2019. More serious outcomes including deaths following oral exposures to buprenorphine have also increased over the same interval for both adult and pediatric patients. Clinically significant rates of respiratory depression in both adult and pediatric patients when taken alone and with additional substances were observed.

Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden

Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs). Utilizing the Premier Healthcare Database, we identified patients > 18 years old, who underwent at least one surgical procedure of interest (i.e., cardiothoracic/vascular, general/colorectal, obstetric/gynecologic, orthopedic, or urologic), and received at least one dose of intravenous morphine, hydromorphone, or fentanyl for acute postoperative pain. The incidence of OIRD and PONV using ICD-9 codes, factors influencing these AEs, length of stay (LOS) and related costs were analyzed. Among 592,127 inpatient stays, rates of respiratory depression ranged from 3% (obstetric/gynecologic) to 17% (cardiothoracic/vascular) and nausea/vomiting from 44% (obstetric/gynecologic) to 72% (general/colorectal). Increased odds of OIRD were associated with older age (cardiothoracic/vascular, general/colorectal, obstetric/gynecologic); obesity, respiratory conditions, and sleep apnea (all surgery groups); opioid dose (cardiothoracic/vascular, general/colorectal, orthopedic); and sedative use after day 1. Increased odds of PONV were associated with younger age, female sex, and major disease severity. When respiratory depression or nausea/vomiting was present versus absent, LOS was significantly longer, and hospital costs were higher. In this analysis, OIRD and PONV were more prevalent than previously reported, were associated with identifiable risk factors, and had substantial effects on resource utilization and costs.

Addition of Intrathecal Morphine for Postoperative Pain Management in Pediatric Spine Surgery: A Meta-analysis.

Meta-analysis. The objective of this study was to determine whether adjunctive intrathecal morphine (ITM) reduces postoperative analgesic consumption following pediatric spine surgery. Previous studies that have tested supplemental ITM to manage pain after pediatric spine surgery have been limited by small sample sizes. A comprehensive search of PubMed, Web of Science, Clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials was performed for clinical trials and observational studies. Time to first analgesic demand, postoperative analgesic use, pain scores, and complication data were abstracted from each study. Mean difference (MD) and 95% confidence interval (CI) were used to compare continuous outcomes and odds ratios (OR) and 95% CI were used for dichotomous outcomes. A total of 5 studies, including 3 randomized controlled trials and 2 retrospective chart reviews, containing 636 subjects, were incorporated into meta-analysis. Subjects that were administered ITM in addition to postoperative analgesics (ITM group) were compared with those receiving postoperative analgesics only (control group). In the ITM group, time to first analgesic demand was longer (MD, 8.79; 95% CI, 4.20-13.37; P<0.001), cumulative analgesic consumption was reduced at 24 hours (MD, -0.40; 95% CI, -0.56 to -0.24; P<0.001), and cumulative analgesic consumption was reduced at 48 hours (MD, -0.43; 95% CI, -0.59 to -0.27; P<0.001). Neither postoperative pain scores at 24 hours (P=0.16) nor 48 hours (P=0.18) were significantly different between ITM and control groups. Rates of respiratory depression, nausea, vomiting, and pruritus were not different between groups (all Ps>0.05). Addition of ITM in pediatric spine surgery produced a potent analgesic effect in the immediate postoperative period. Patients administered ITM did not request opiates as early as control and consumed fewer opiates by the second postoperative day. Furthermore, use of ITM did not increase complications such as respiratory depression, nausea, vomiting, or pruritus.

(137) Addition of Intrathecal Morphine to Manage Postoperative Pain in Pediatric Spine Surgery: A Meta-Analysis of Existing Studies

Whether intrathecal morphine (ITM) can be used as an adjunct to reduce postoperative pain without increasing the rate of complications following pediatric spine surgery remains uncertain. Previous studies have been limited by conflicting results or small sample sizes. Therefore, a meta-analysis of existing clinical trials and chart reviews was performed. The following databases were searched: PubMed, Clarivate Analytics Web of Science, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. Data for time to first analgesic demand, postoperative analgesic consumption, and complications were collected and analyzed. Mean difference (MD) and 95% confidence interval (CI) were used to compare time to first analgesic demand and postoperative analgesic consumption; Odds Ratio (OR) and 95% CI used to compare respiratory depression, nausea, vomiting, and pruritus. After irrelevant articles were discarded, 5 articles (3 randomized controlled trials and 2 retrospective chart reviews) including 636 subjects were analyzed. Patients administered ITM requested postoperative analgesics later compared to control (MD: 8.79, 95% CI: 4.20 to 13.37, p 0.05). These findings suggest that addition of ITM reduces postoperative analgesic requirements in pediatric spine surgery patients without increasing rates of respiratory depression, nausea, vomiting, or pruritus. Future high-quality clinical trials are needed to determine the optimal dose of ITM in pediatric spine surgery.

Intravenous Olanzapine for the Management of Agitation: Review of the Literature.

Objective: The purpose of this review is to summarize the current evidence of the off-label use of intravenous (IV) olanzapine and discuss its risks versus benefits for the management of agitation. Data Sources: A literature search was conducted to gather relevant data regarding IV use of olanzapine for the management of acute agitation. PubMed, EMBASE, MEDLINE, and IPA were searched using the keywords and MESH terms: olanzapine, intravenous, IV, off-label, and agitation. Study Selection and Data Extraction: All case reports, and retrospective and prospective studies evaluating the efficacy and safety of IV olanzapine administration for agitation from January 2004 to December 2018 were analyzed. Data Synthesis: Doses from 2.5 to 10 mg given as an IV bolus (maximum dose of 30 mg/d) have been administered. Rescue medications such as droperidol or parenteral benzodiazepines are sometimes coadministered to assist with achieving adequate sedation. Prospective studies demonstrate efficacy similar to droperidol in achieving adequate sedation within 10 minutes and similar time to onset of sedation. Rates of respiratory depression and airway obstruction are low and similar to that of comparative agents, including intramuscular olanzapine. Relevance to Patient Care and Clinical Practice: This review evaluated the off-label use of IV olanzapine to manage agitation based on case reports, and retrospective and prospective data. Conclusions: The use of IV olanzapine remains controversial in the absence of clear evidence evaluating safety and efficacy. Future studies are warranted comparing IV olanzapine with more commonly utilized and Food and Drug Administration-approved treatment modalities for acute agitation in the emergency department and other settings.

Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.

Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.

Hospitalization costs and resource allocation in cholecystectomy with use of intravenous versus oral acetaminophen

Objective: To evaluate intravenous (IV) acetaminophen (APAP) vs oral APAP use as adjunctive analgesics in cholecystectomy patients by comparing associated hospital length of stay (LOS), hospital costs, opioid use, and rates of nausea/vomiting, respiratory depression, and bowel obstruction.Methods: We conducted a retrospective analysis of the Premier Database (January 2012 to September 2015) including cholecystectomy patients who received either IV APAP or oral APAP. Differences in LOS, hospitalization costs, mean daily morphine equivalent dose (MED), and potential opioid-related adverse events were estimated. Multivariable logistic regression was performed for the binary outcomes and instrumental variable regressions, using the quarterly rate of IV APAP use for all hospitalizations by hospital as the instrument in two-stage least squares regressions for continuous outcomes. Models were adjusted for patient demographics, clinical risk factors, and hospital characteristics.Results: Among 61,017 cholecystectomy patients, 31,133 (51%) received IV APAP. Subjects averaged 51 and 57 years of age, respectively, in the IV and oral APAP cohorts. In the adjusted models, IV APAP was associated with 0.42 days shorter LOS (95% CI = –0.58 to –0.27; p < .0001), $1,045 lower hospitalization costs (95% CI = –$1,521 to –$569; p < .0001), 2 mg lower average daily MED (95% CI = –3 mg to –0.9 mg; p = .0005), and lower rates of respiratory depression (odds ratio [OR] = 0.89, 95% CI = 0.82–0.97; p = .006), and nausea and vomiting (OR = 0.86, 95% CI = 0.86–0.86; p < .0001).Conclusions: In patients having cholecystectomy, the addition of IV APAP to perioperative pain management is associated with shorter LOS, lower costs, reduced opioid use, and less frequent nausea/vomiting and respiratory depression compared to oral APAP. These findings should be confirmed in a prospective study comparing IV and oral APAP.

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial

BackgroundIntrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question.Methods/design‘The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine’ trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients.Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor’s accuracy for detecting respiratory depression.DiscussionThe trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety.Trial registrationClinicalTrials.gov, ID: NCT02885948. Registered retrospectively on 4 July 2016.Protocol Version 2.0, 3 April 2017.Protocol identification (code or reference number): UCDCRC/15/006EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.

Clinical effects of unintentional pediatric buprenorphine exposures: experience at a single tertiary care center

Context: Exploratory buprenorphine ingestions in young children have been associated with clinically significant toxicity. However, detailed data on the clinical presentation and management of these patients are lacking. In an attempt to obtain more comprehensive data, we sought to examine a single center cohort of patients with report of buprenorphine exposure and provide descriptive analysis of rates of respiratory depression, time to respiratory depression, interventions, disposition, and outcomes.Study design: We performed a retrospective cohort study at a single pediatric tertiary care center of children between the age of 6 months and 7 years of age hospitalized between 1 January 2006 and 1 September 2014 with report of buprenorphine or buprenorphine/naloxone exposure. Patients with possible exposure to more than one agent were excluded. We extracted clinical findings, including time to respiratory depression, interventions, and disposition from the medical record.Results: Eighty-eight patients met the inclusion criteria. Seven patients were excluded. The median age was 24 months [IQR 18–30]. 20 patients (23%) received activated charcoal while 48 (55%) were treated with naloxone. 36 (41%) patients were admitted to the ICU. Observed clinical effects included respiratory depression (83%), oxygen saturation by pulse oximetry (SpO2) < 93% (28%), depressed mental status (80%), miosis (77%), and emesis (45%). Median time from exposure to respiratory depression was 263 min [IQR 105–486]. The median hospital length of stay was 22 h [IQR 20–26] and was positively associated with estimated exposure dose (p = 0.002).Conclusion: Pediatric patients exposed to buprenorphine are likely to exhibit signs and symptoms of opioid toxicity, including respiratory depression, altered mental status and miosis. Although the majority of patients developed signs of clinical toxicity within 8 h of reported exposure, the optimum duration of monitoring remains unclear.

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society.

The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events associated with intravenous anticonvulsant drug administration in adults with convulsive status epilepticus (Level A). The rate of respiratory depression in patients with convulsive status epilepticus treated with benzodiazepines is lower than in patients with convulsive status epilepticus treated with placebo indicating that respiratory problems are an important consequence of untreated convulsive status epilepticus (Level A). When both are available, fosphenytoin is preferred over phenytoin based on tolerability but phenytoin is an acceptable alternative (Level A). In adults, compared to the first therapy, the second therapy is less effective while the third therapy is substantially less effective (Level A). In children, the second therapy appears less effective and there are no data about third therapy efficacy (Level C). The evidence was synthesized into a treatment algorithm. Despite the paucity of well-designed randomized controlled trials, practical conclusions and an integrated treatment algorithm for the treatment of convulsive status epilepticus across the age spectrum (infants through adults) can be constructed. Multicenter, multinational efforts are needed to design, conduct and analyze additional randomized controlled trials that can answer the many outstanding clinically relevant questions identified in this guideline.

Hamilton Acute Pain Service Safety Study

Although intravenous patient-controlled analgesia opioids and epidural analgesia offer improved analgesia for postoperative patients treated on an acute pain service, these modalities also expose patients to some risk of serious morbidity and even mortality. Root cause analysis, a process for identifying the causal factor(s) that underlie an adverse event, has the potential to identify and address system issues and thereby decrease the chance of recurrence of these complications. This study was designed to compare the incidence of adverse events on an acute pain service in three hospitals, before and after the introduction of a formal root cause analysis process. The "before" cohort included all patients with pain from February 2002 to July 2007. The "after" cohort included all patients with pain from January 2009 to December 2009. A total of 35,384 patients were tracked over the 7 yr of this study. The after cohort showed significant reductions in the overall event rate (1.47 vs. 2.35% or 1 in 68 vs. 1 in 42, the rate of respiratory depression (0.41 vs. 0.71%), the rate of severe hypotension (0.78 vs. 1.34%), and the rate of patient-controlled analgesia pump programming errors (0.0 vs. 0.08%). Associated with these results, the incidence of severe pain increased from 6.5 to 10.5%. To achieve these results, 26 unique recommendations were made of which 23 being completed, 1 in progress, and 2 not completed. Formal root cause analysis was associated with an improvement in the safety of patients on a pain service. The process was effective in giving credibility to recommendations, but addressing all the action plans proved difficult with available resources.

This Month In: Anesthesiology

This Month In: Anesthesiology

An integrative review of the side effects related to the use of magnesium sulfate for pre-eclampsia and eclampsia management

BackgroundPre-eclampsia/eclampsia is one of the most common causes of maternal and perinatal morbidity and mortality in low and middle income countries. Magnesium sulfate is the drug of choice for prevention of seizures as part of comprehensive management of the disease. Despite the compelling evidence for the effectiveness of magnesium sulfate, concern has been expressed about its safety and potential for toxicity, particularly among providers in low- and middle-income countries. The purpose of this review was to determine whether the literature published in these global settings supports the concerns about the safety of use of magnesium sulfate.MethodsAn integrative review of the literature was conducted to document the known incidences of severe adverse reactions to magnesium sulphate, and specific outcomes of interest related to its use. All types of prospective clinical studies were included if magnesium sulfate was used to manage pre-eclampsia or eclampsia, the study was conducted in a low- or middle-income country, and the study included the recording of the incidence of any adverse side effect resulting from magnesium sulfate use.ResultsA total of 24 studies that compared a magnesium sulfate regimen against other drug regimens and examined side effects among 34 subject groups were included. The overall rate of absent patellar reflex among all 9556 aggregated women was 1.6%, with a range of 0-57%. The overall rate of respiratory depression in 25 subject groups in which this outcome was reported was 1.3%, with a range of 0–8.2%. Delay in repeat administration of magnesium sulfate occurred in 3.6% of cases, with a range of 0-65%. Calcium gluconate was administered at an overall rate of less than 0.2%. There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate among the 9556 women in the 24 studies.ConclusionConcerns about safety and toxicity from the use of magnesium sulfate should be mitigated by findings from this integrative review, which indicates a low incidence of the most severe side effects, documented in studies that used a wide variety of standard and modified drug regimens. Adverse effects of concern to providers occur infrequently, and when they occurred, a delay of repeat administration was generally sufficient to mitigate the effect. Early screening and diagnosis of the disease, appropriate treatment with proven drugs, and reasonable vigilance for women under treatment should be adopted as global policy and practice.

The Effect of the Assignment of a Pre-Sedation Target Level on Procedural Sedation Using Propofol

The goal of this study was to determine if there is a difference in the achieved depth of sedation, the rate of respiratory depression, procedural difficulty, or patient perceived pain or recall between patients randomized to a pre-procedural target sedation level of moderate or deep procedural sedation using propofol during the reduction of fractures and dislocations in the Emergency Department (ED). This was a randomized, prospective study of adults undergoing procedural sedation (PS) with propofol for fracture or dislocation reduction in the ED between July 2003 and March 2004. Patients were randomized to a target sedation level of moderate or deep, using American Society of Anesthesiologists’ definitions. Doses, vital signs, nasal end tidal CO 2 (ETCO 2), pulse oximetry, and bispectral EEG analysis (BIS) scores were recorded. Respiratory depression was defined as a change in ETCO 2 >10, an oxygen saturation of <90% at any time, or an absent ETCO 2 waveform at any time. After the procedure, patients were asked if they perceived any pain or had any recall of the procedure. Physicians were asked to rate the difficulty of completing the reduction using a 100-mm visual analog scale (VAS). Respiratory depression rates were compared with chi-square tests, BIS and VAS scores were compared with t tests. Seventy-five patients were enrolled, 39 randomized to the target of moderate PS and 36 to the target of deep PS. No significant complications were noted. There were 25/36 (69%) of the patients assigned to the deep sedation target group who actually achieved a deep level of sedation and 21/39 (54%) of the patients assigned to the moderate sedation target group who actually achieved a moderate level of sedation ( p = 0.40). Respiratory depression was seen in 19/39 (49%) patients with the moderate PS target and 18/36 (50%) with the deep PS target ( p = 0.91). The mean minimum recorded BIS score was 67.7 (95% confidence interval [CI] 62.2–73.3) for the moderate PS target group and 59.2 (95% CI 55.1–64.2) for the deep PS target group ( p = 0.03). There were 12/39 (31%) in the moderate PS target group and 4/36 (11%) in the deep PS target group who reported pain with or recall of the procedure ( p = 0.04). The mean physician VAS for procedural difficulty was 34.0 (95% CI 23.7–44.3) for the moderate PS group and 28.8 (95% CI 18.4–39.2) for the deep PS group ( p = 0.46). In this study, the assignment of a pre-procedural target sedation level of moderate or deep PS did not influence the level of sedation achieved, the rate of respiratory depression, the occurrence of complications, the time to return of baseline mental status, or the success of the procedure. It does not seem that the assignment of a pre-procedural target sedation level is an effective means of changing the outcome of ED PS.

A Comparison of a Fentanyl, Morphine, and Hydromorphone Patient-Controlled Intravenous Delivery for Acute Postoperative Analgesia: A Multicenter Study of Opioid-Induced Adverse Reactions

Patient-controlled analgesia (PCA) is a widely used delivery system for intravenous (IV) administration of opioids during acute post-operative pain management. Various opioids have been used for IV PCA including morphine, meperidine, hydromorphone, and fentanyl. Morphine is by far the most commonly used opioid in this setting, yet the selection of morphine as the primary opioid is based largely on tradition. Meperidine should not be considered in the PCA armamentarium due to the associated risk of central nervous system toxicity from its metabolite normeperidine. The objective of this study is to compare the rate of opioid-induced adverse reactions among three IV PCA opioids, fentanyl, morphine, and hydromorphone, in acute post-operative pain management. Although morphine is the most frequently used opioid, the results from three US hospitals indicate that fentanyl IV PCA had a significantly lower rate of common opioid induce adverse reactions (nausea/vomiting, pruritus, urinary retention, or sedation), when compared to IV PCA morphine and hydromorphone in acute post-operative pain management. The median pain score on post-operative day-1 and -2 was significantly lower in fentanyl IV PCA group. The quantity of opioid in each group was not significantly different when converted to an analgesic equivalence. Morphine and hydromorphone IV PCA were no different in rates of adverse reactions in any area; although, the hydromorphone group trended toward a lower pruritus and urinary retention rate compared to morphine, but this was not statistically significant. The rate of respiratory depression was not significantly different between the three opioids. Fentanyl IV PCA is an under used opioid for post-operative acute-pain management and should be considered more often due to the lower adverse reaction profile.