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Respiratory Depression (respiratory + depression)

Distribution by Scientific Domains

Medical Sciences	90%
Life Sciences	6%

Distribution within Medical Sciences

Anesthesia & Pain Management	41%
Neurology	6%
General & Introductory Veterinary Medicine	4%
7 Other Subdomains	39%

Selected Abstracts

Comparison of Routes of Flumazenil Administration to Reverse Midazolam-induced Respiratory Depression in a Canine Model

ACADEMIC EMERGENCY MEDICINE, Issue 5 2000
Melanie S. Heniff MD
ABSTRACT Objective: To determine whether flumazenil, a drug used to reverse benzodiazepine-induced respiratory depression and approved only for IV use, is effective by alternative routes. Methods: A randomized, controlled, nonblinded, crossover canine trial was performed to evaluate reversal of midazolam-induced respiratory depression by flumazenil when administered by alternative routes. Mongrel dogs were sedated with thiopental 19 mg/kg IV, then tracheally intubated. With the dogs spontaneously breathing, tidal volume, end-tidal CO2, and O2 saturation were observed until a stable baseline was achieved. Incremental doses of midazolam were administered until respiratory depression (30% decline in tidal volume, 10% decrease in O2 saturation, and 15% increase in end-tidal CO2) occurred. Flumazenil was administered by a randomly selected route [0.2 mg followed 1 minute later by 0.3 mg IV, sublingual (SL) or intramuscular (IM); or 1 mg followed 1 minute later by 1.5 mg per rectum (PR)]. Time to return to baseline respiratory functions was recorded ("time to reversal"). Each of 10 dogs was studied using all 4 routes of flumazenil administration with a washout period of at least 7 days. An additional dog served as a control (no flumazenil). Results: The control time to reversal was 1,620 seconds. The IV route was significantly faster (mean 120 ± 24.5 sec) than the other 3 routes (p < 0.005). The SL route was the second fastest (mean 262 ± 94.5 sec), the IM route was the third fastest (mean 310 ± 133.7 sec), and the PR route was the slowest (mean 342 ± 84.4 sec). The SL, IM, and PR routes did not differ significantly from one another. Conclusions: Flumazenil administered by all 4 routes reversed midazolam-induced respiratory depression in a dog model. For the selected dosages used, the IV route was significantly faster than all 3 other routes, and SL was the second fastest. [source]

,Respiratory depression in children receiving diazepam for acute seizures: a prospective study'

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2000
Robert L Kriel MD
No abstract is available for this article. [source]

Bispectral Electroencephalographic Analysis of Patients Undergoing Procedural Sedation in the Emergency Department

ACADEMIC EMERGENCY MEDICINE, Issue 6 2003
James R. Miner MD
Abstract Objective: To determine whether there is a correlation between the level of sedation achieved during procedural sedation (PS) in the emergency department as determined by bispectral electroencephalographic (EEG) analysis (BIS) and the rate of respiratory depression (RD), the patient's perception of pain, recall of the procedure, and satisfaction. Methods: This was a prospective observational study conducted in an urban county hospital of adult patients undergoing PS using propofol, methohexital, etomidate, and the combination of fentanyl and midazolam. Consenting patients were monitored by vital signs, pulse oximetry, nasal-sample end-tidal carbon dioxide (ETCO2), and BIS monitors during PS. Respiratory depression (RD) was defined as an oxygen saturation <90%, a change from baseline ETCO2 of >10 mm Hg, or an absent ETCO2 waveform at any time during the procedure. After the procedure, patients were asked to complete three 100-mm visual analog scales (VASs) concerning their perception of pain, recall of the procedure, and satisfaction with the procedure. Patients were divided into four groups based on the lowest BIS score recorded during the procedure, group 1, >85; group 2, 70,85; group 3, 60,69; group 4, <60. Rates of RD and VAS outcomes were compared between groups using chi-square statistics. Results: One hundred eight patients were enrolled in the study. No serious adverse events were noted. RD was seen in three of 14 (21.4%) of the patients in group 1, seven of 34 (20.6%) in group 2, 16 of 26 (61.5%) in group 3, and 18 of 34 (52.9%) in group 4. The rate of RD in patients in group 2 was not significantly different from that in group 1 (p = 0.46). The rate of RD in group 2 was significantly lower than that in groups 3 (p = 0.0003) and 4 (p = 0.006). For the VAS data, when group 1 was compared with the combined groups 2, 3, and 4, it had significantly higher rates of pain (p = 0.003) and recall (p = 0.001), and a dissatisfaction rate (p = 0.085) that approached significance. When groups 2, 3, and 4 were compared with chi-square test, there was not a significant difference in pain (p = 0.151), recall (p = 0.27), or satisfaction (p = 0.25). Conclusions: Patients with a lowest recorded BIS score between 70 and 85 had the same VAS outcomes as more deeply sedated patients and the same rate of RD as less deeply sedated patients. This range of scores represented the optimally sedated patients in this study. [source]

PRECLINICAL STUDY: Mechanisms of respiratory insufficiency induced by methadone overdose in rats

ADDICTION BIOLOGY, Issue 1 2010
Lucie Chevillard
ABSTRACT Methadone may cause respiratory depression. We aimed to understand methadone-related effects on ventilation as well as each opioid-receptor (OR) role. We studied the respiratory effects of intraperitoneal methadone at 1.5, 5, and 15 mg/kg (corresponding to 80% of the lethal dose-50%) in rats using arterial blood gases and plethysmography. OR antagonists, including intravenous 10 mg/kg-naloxonazine at 5 minutes (mu-OR antagonist), subcutaneous 30 mg/kg-naloxonazine at 24 hours (mu1-OR antagonist), 3 mg/kg-naltrindole at 45 minutes (delta-OR antagonist) and 5 mg/kg-Nor-binaltorphimine at 6 hours (kappa-OR antagonist) were pre-administered. Plasma concentrations of methadone enantiomers were measured using high-performance liquid chromatography coupled to mass-spectrometry. Methadone dose-dependent inspiratory time (TI) increase tended to be linear. Respiratory depression was observed only at 15 mg/kg and characterized by an increase in expiratory time (TE) resulting in hypoxemia and respiratory acidosis. Intravenous naloxonazine completely reversed all methadone-related effects on ventilation, while subcutaneous naloxonazine reduced its effects on pH (P < 0.05), PaCO2 (P < 0.01) and TE (P < 0.001) but only partially on TI (P < 0.001). Naltrindole reduced methadone-related effects on TE (P < 0.001). Nor-binaltorphimine increased methadone-related effects on pH and PaO2 (P < 0.05) Respiratory effects as a function of plasma R -methadone concentrations showed a decrease in PaO2 (EC50: 1.14 µg/ml) at lower concentrations than those necessary for PaCO2 increase (EC50: 3.35 µg/ml). Similarly, increased TI (EC50: 0.501 µg/ml) was obtained at lower concentrations than those for TE (EC50: 4.83 µg/ml). Methadone-induced hypoxemia is caused by mu-ORs and modulated by kappa-ORs. Additionally, methadone-induced increase in TE is caused by mu1- and delta-opioid receptors while increase in TI is caused by mu-ORs. [source]

Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)

PAIN PRACTICE, Issue 4 2008
Joseph Pergolizzi MD
,,Abstract Summary of consensus: 1.,The use of opioids in cancer pain:, The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities,including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia,and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation,fentanyl and buprenorphine,fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2.,The use of opioids in noncancer-related pain:, Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3.,The use of opioids in neuropathic pain:, The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4.,The use of opioids in elderly patients with impaired hepatic and renal function:, Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that,except for buprenorphine,doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5.,Opioids and respiratory depression:, Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6.,Opioids and immunosuppression:, Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7.,Safety and tolerability profile of opioids:, The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.,, [source]

Intravenous lidocaine for status epilepticus during childhood

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2006
Shin-ichiro Hamano MD;
The clinical efficacy of lidocaine for convulsive status epilepticus in 53 convulsive episodes was examined in 37 children (17 males, 20 females). Mean age of patients receiving lidocaine was 3 years 7 months (SD 3y 5mo). Lidocaine administration achieved control of status epilepticus in 19 of 53 convulsive episodes (35.8%). Seizures ceased within 5 minutes of lidocaine administration in all 19 patients who were responsive to the drug. Regarding aetiology of status epilepticus and types of seizures, there was no statistical difference in effectiveness. Mild decrease of oxygen saturation, monitored by pulse oximetry, was observed in one patient, which improved by oxygenation using a mask. Lidocaine is a useful anticonvulsive agent; however, the response rate to lidocaine appears to be quite low, as less than half of the seizures were effectively controlled by lidocaine. Favourable properties of the drug include prompt responses, less alteration of consciousness, and fewer adverse effects, including less respiratory depression. [source]

Bispectral Electroencephalographic Analysis of Patients Undergoing Procedural Sedation in the Emergency Department

PRECLINICAL STUDY: Mechanisms of respiratory insufficiency induced by methadone overdose in rats

Comparison of Routes of Flumazenil Administration to Reverse Midazolam-induced Respiratory Depression in a Canine Model

Comparison of spinal anesthesia with general anesthesia on morphine requirement after abdominal hysterectomy

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009
L. MASSICOTTE
Purpose: The aim of this study was to compare morphine consumption with patient-controlled analgesia (PCA) between spinal anesthesia (SA) (bupivacaine, morphine and fentanyl) and general anesthesia (GA) (sufentanil) after an abdominal hysterectomy. Methods: Forty women were randomly assigned to receive SA with bupivacaine 15 mg, 0.15 mg of intrathecal morphine and 15 ,g of fentanyl or GA with sufentanil, both combined with PCA. The primary outcome was morphine consumption with the PCA device. The secondary outcomes were post-operative pain at rest and under stress on a visual analog scale, nausea, pruritus and respiratory depression on a standardized scale. Outcome measures were recorded at 6, 12, 18, 24 and 48 h post-anesthesia. The duration of post-anesthesia care unit (PACU) and hospital stay were recorded. Results: Patients in the SA group consumed at least two times less morphine at each time interval than the GA group: at 48 h, they used 19 ± 17 vs. 81 ± 31 mg (P<0.0001). Post-operative pain at rest was lower in the SA group until the 18th hour and under stress until the 48th. There was more sedation in the GA group until the 18th hour. Little difference was observed in the incidence of pruritus. Nausea was more intense at the 6th hour in the GA group. There was no difference in the respiratory rate. The duration of PACU stay was shorter for the SA group (52 ± 9 vs. 73 ± 11 min, P<0.0001) as was the duration of hospital stay (2.2 ± 0.4 vs. 3.3 ± 0.7 days, P=0.01). Conclusions: It is concluded that intrathecal morphine 0.15 mg with 15 ,g of fentanyl decreases post-operative pain and morphine consumption by PCA without increasing adverse reactions for women undergoing an abdominal hysterectomy. [source]

Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgery

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2009
A. PESONEN
Background: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients. Methods: Thirty (,75 years, gender M9/F21) and 20 (,60 years, gender M20/F0) patients scheduled to undergo cardiac surgery. A standard anesthesia with fentanyl as an opioid was used. Fentanyl plasma concentrations were measured at the end of surgery and 2 h later. After tracheal extubation, when the pain intensity was at least moderate, blood samples for fentanyl and oxycodone plasma concentration measurements were taken. Thereafter, oxycodone hydrochloride 0.05 mg/kg i.v. was administered. After 15 and 45 min, pain intensity, sedation and oxycodone plasma concentration were determined. This test protocol was repeated twice. Results: The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients (5.7±2.2 vs. 3.8±1.2 ng/ml, P=0.001). The plasma concentrations of oxycodone were comparable between the groups. The interval between the second and the third oxycodone dose was longer in the elderly patients (P=0.036). Pain intensity on the verbal rating scale was lower at the 45-min assessment point after all three oxycodone test doses (P=0.008) and sedation scores were significantly higher after the third dose in the elderly patients (P=0.035). Conclusions: In elderly patients, the plasma concentration of fentanyl was higher but plasma levels of oxycodone were at a similar level compared with middle-aged patients. However, the elderly patients had less pain and were more sedated after doses of oxycodone. [source]

SOMA (carisoprodol) toxicity in a dog

JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2005
Stephen G. Lane DVM
Abstract Objective: To describe a case of SOMA intoxication in a dog. Case summary: A 13-year-old, 25 kg, female spayed Australian shepherd presented to the emergency service after ingestion of ten to fifteen 350 mg tablets of SOMA (carisoprodol), a muscle relaxant used for back pain in humans. Toxic effects of the drug in this dog included mild sinus tachycardia, respiratory depression, seizures, and ataxia. The dog's mentation progressively deteriorated from depressed to comatose within 1 hour after admission. Treatment on initial presentation consisted of induction of emesis while the dog still had a gag reflex, administration of activated charcoal, oxygen therapy, and supportive care. The dog was discharged to the owner prior to full recovery (4 days later). New or unique information provided: This is the first known report of carisoprodol intoxication in the dog. [source]

Pharmacokinetic and pharmacodynamic properties of metomidate in turbot (Scophthalmus maximus) and halibut (Hippoglossus hippoglossus)

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2003
M. K. Hansen
Metomidate was administered to halibut (Hippoglossus hippoglossus) and turbot (Scophthalmus maximus) intravenously at a dose of 3 mg/kg bodyweight, as a bath treatment at a dose of 9 mg/L water for 5 min to study the disposition of metomidate, and as bath treatment (9 mg/L) for 10 min to study the absorption and effect of metomidate on respiration and balance/motor control. Additionally, turbot were given metomidate orally at a dose of 7 mg/kg. The studies were performed in seawater at a temperature of 10.3 ± 0.4 °C (halibut) and 18.0 ± 0.3 °C (turbot). Pharmacokinetic modeling of the data showed that metomidate had shorter elimination half-life and higher plasma concentrations in turbot compared with halibut, both species displaying a rapid uptake, distribution and excretion. Following intravenous administration, the volumes of distribution at steady state (Vd(ss)) were 0.21 L/kg (halibut) and 0.44 L/kg (turbot). Plasma clearances (Cl) were 0.099 L/h·kg in halibut and 0.26 L/h·kg in turbot and the elimination half-lives (t½,z) were calculated to be 5.8 h and 2.2 h in halibut and turbot, respectively. Mean residence times (MRT) were 2.2 h in halibut and 1.7 h in turbot. Following oral administration, the t½,z was 3.5 h in turbot. The maximum plasma concentration (Cmax) was 7.8 mg/L in turbot 1 h after administration. The oral bioavailability (F) was calculated to 100% in turbot. Following 5 min bath the maximum plasma concentrations (Cmax), which were observed immediately after end of the bath, were 9.5 mg/L and 13.3 mg/L in halibut and turbot, respectively. Metomidate rapidly immobilized the fish, with respiratory depression, reduced heart rate, and loss of balance/motor control within 1 min (mean). Recovery was slow, with resumed balance/motor control after 26.4 min. Opercular respiration movements were resumed more rapidly with a recorded mean of 1.7 min. Oral administration was demonstrated to be a way of immobilizing fish, for example in large aquariums, without exposing them to unwanted stress. [source]

Registered nurse-administered propofol sedation for endoscopy

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2004
S. C. Chen
Summary Propofol has several attractive properties that render it a potential alternative sedative agent for endoscopy. Compared with meperidine and midazolam, it has an ultra-short onset of action, short plasma half-life, short time to achieve sedation, faster time to recovery and discharge, and results in higher patient satisfaction. Shorter times to achieve sedation enhance efficiency in the endoscopy unit. Multiple studies have documented the safe administration of propofol by non-anaesthesiologists. Administration by registered nurses is more cost-effective than administration by anaesthesiologists. However, the administration of propofol by a registered nurse supervised only by the endoscopist is controversial because the drug has the potential to produce sudden and severe respiratory depression. More information is needed on how training nurses and endoscopists should proceed to give propofol, as well as the optimal level of monitoring to ensure the safety of nurse-administered propofol. [source]

Morphine-6-glucuronide: Actions and mechanisms

MEDICINAL RESEARCH REVIEWS, Issue 5 2005
Gavin J. Kilpatrick
Abstract Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side-effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the µ-opioid receptor. The differences for which there is a reasonable consensus in the literature can be summarized as: (1) Morphine has a slightly higher affinity for the µ-opioid receptor than M6G, (2) M6G shows a slightly higher efficacy at the µ-opioid receptor, (3) M6G has a lower affinity for the ,-opioid receptor than morphine, and (4) M6G has a very different absorption, distribution, metabolism, and excretion (ADME) profile from morphine. However, none of these are adequate alone to explain the clinical differences between M6G and morphine. The ADME differences are perhaps most likely to explain some of the differences but seem unlikely to be the whole story. Further work is required to examine further the profile of M6G, notably whether M6G penetrates differentially to areas of the brain involved in pain and those involved in nausea, vomiting, and respiratory control or whether µ-opioid receptors in these brain areas differ in either their regulation or pharmacology. © 2005 Wiley Periodicals, Inc. Med Res Rev [source]

Gender differences in drug effects: implications for anesthesiologists

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2003
H. Pleym
Background:, The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need for research. Methods:, Basis for this paper was obtained by Medline searches using the key words ,human' and ,gender' or ,sex,' combined with individual drug names. The reference lists of these papers were further checked for other relevant studies. Results:, Females have 20,30% greater sensitivity to the muscle relaxant effects of vecuronium, pancuronium and rocuronium. When rapid onset of or short duration of action is very important, gender-modified dosing may be considered. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30,40% in males compared with females in order to achieve similar recovery times. Females are more sensitive than males to opioid receptor agonists, as shown for morphine as well as for a number of kappa (OP2) receptor agonists. On this basis, males will be expected to require 30,40% higher doses of opioid analgesics than females to achieve similar pain relief. On the other hand, females may experience respiratory depression and other adverse effects more easily if they are given the same doses as males. Conclusion:, These examples illustrate that gender should be taken into account as a factor that may be predictive for the dosage of several anesthetic drugs. Moreover, there is an obvious need for more research in this area in order to further optimize drug treatment in anesthesia. [source]

Treatment of restless legs syndrome: An evidence-based review and implications for clinical practice,,

MOVEMENT DISORDERS, Issue 16 2008
Claudia Trenkwalder MD
Abstract Only in the last three decades, the restless legs syndrome (RLS) has been examined in randomized controlled trials. The Movement Disorder Society (MDS) commissioned a task force to perform an evidence-based review of the medical literature on treatment modalities used to manage patients with RLS. The task force performed a search of the published literature using electronic databases. The therapeutic efficacy of each drug was classified as being either efficacious, likely efficacious, investigational, nonefficacious, or lacking sufficient evidence to classify. Implications for clinical practice were generated based on the levels of evidence and particular features of each modality, such as adverse events. All studies were classed according to three levels of evidence. All Level-I trials were included in the efficacy tables; if no Level-I trials were available then Level-II trials were included or, in the absence of Level-II trials, Level-III studies or case series were included. Only studies published in print or online before December 31, 2006 were included. All studies published after 1996, which attempted to assess RLS augmentation, were reviewed in a separate section. The following drugs are considered efficacious for the treatment of RLS: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Drugs considered likely efficacious are rotigotine, bromocriptine, oxycodone, carbamazepine, valproic acid, and clonidine. Drugs that are considered investigational are dihydroergocriptine, lisuride, methadone, tramadol, clonazepam, zolpidem, amantadine, and topiramate. Magnesium, folic acid, and exercise are also considered to be investigational. Sumanirole is nonefficacious. Intravenous iron dextran is likely efficacious for the treatment of RLS secondary to end-stage renal disease and investigational in RLS subjects with normal renal function. The efficacy of oral iron is considered investigational; however, its efficacy appears to depend on the iron status of subjects. Cabergoline and pergolide (and possibly lisuride) require special monitoring due to fibrotic complications including cardiac valvulopathy. Special monitoring is required for several other medications based on clinical concerns: opioids (including, but not limited to, oxycodone, methadone and tramadol), due to possible addiction and respiratory depression, and some anticonvulsants (particularly, carbamazepine and valproic acid), due to systemic toxicities. © 2008 Movement Disorder Society [source]

UNINTENTIONAL OVERDOSE WITH INTRATHECAL ZICONOTIDE

PAIN MEDICINE, Issue 2 2002
Article first published online: 4 JUL 200
Steven G. Charapata MD, Research Medical Center, Kansas City, MO; David Ellis MD, PhD, Elan Pharmaceuticals, South San Francisco, CA Ziconotide is a novel, N-type, voltage-sensitive calcium channel (VSCC) blocker, with well-documented efficacy as an intrathecal (IT) analgesic. Ziconotide has been administered to over 1000 chronic pain patients in nine clinical trials. Over 350 patients have been on ziconotide IT therapy for more than three months in a long-term safety and tolerability study. Common adverse events for ziconotide include dizziness, nausea, nystagmus, abnormal gait, constipation, urinary retention, somnolence, postural hypotension, vomiting, confusion and abnormal vision. Ziconotide adverse events are recognizable, reversible and manageable, by dose adjustment and slow dose titration. Case reports of unintentional overdose in six chronic pain patients treated with IT ziconotide are presented. These unintentional overdoses were attributable to pump programming or dilution errors; none were lethal. The patient who received the highest overdose was administered 31 mcg/hr over 24 hours, or nearly 750 mcg ziconotide, total. This hourly dose rate is 300-fold the current recommended initial dose rate of 0.1 mcg/hr. This patient was sedated, but arousable; vital signs were stable and patient had no change in blood pressure. His symptoms resolved within 24 hours. His Visual Analog Score of Pain Intensity (VASPI) was reduced from 82 at baseline to 2.5 at the end of the titration period. The patient elected to continue in the long-term IT ziconotide study. The other 5 cases of inadvertent overdose were less severe, with dose rate at 5 mcg/hr or less. Associated adverse events also resolved within 24-hours of discontinuing ziconotide infusion. Unlike an unintentional overdose with IT morphine, which slows respiration and could potentially lead to hypoxia, coma or death; ziconotide does not produce respiratory depression. No tolerance to the analgesic effect of ziconotide, or withdrawal symptoms after discontinuation of the drug have been reported. Ziconotide has a wide margin of safety as an IT analgesic. [source]

Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)

Bradycardia and asystolic cardiac arrest during spinal anaesthesia: A report of five cases

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2000
R. Z. Løvstad
Sudden, severe bradycardia/asystolic cardiac arrest are considered infrequent, but are certainly the most serious complications of spinal anaesthesia. We report four cases of primary asystole and one of severe bradycardia in young to middle-aged, healthy patients scheduled for minor surgery at the day surgery unit. Bradycardia/asystole were not related to respiratory depression or hypoxaemia/hypercarbia; they occurred at different time intervals after the onset of spinal anaesthesia (10,70 min) and, apparently, were not dependent on the level of sensory block, which varied between T3 and T8. One patient was nauseated seconds before the asystole, otherwise there was no warning signs. All the patients were easily resuscitated with the prompt administration of atropine and ephedrine and, in the case of cardiac arrest, cardiac massage and ventilation with oxygen. One patient was treated with a small dose of adrenaline. Four patients had the surgery, as planned; one had the surgery postponed. All the patients were discharged from hospital in good health and did not suffer any sequelae. [source]

APA national audit of pediatric opioid infusions

PEDIATRIC ANESTHESIA, Issue 2 2010
FFPMRCA, FRCPCH, NEIL S. MORTON MD
Summary Introduction:, A prospective audit of neonates, infants, and children receiving opioid infusion techniques managed by pediatric acute pain teams from across the United Kingdom and Eire was undertaken over a period of 17 months. The aim was to determine the incidence, nature, and severity of serious clinical incidents (SCIs) associated with the techniques of continuous opioid infusion, patient-controlled analgesia, and nurse-controlled analgesia in patients aged 0,18. Methods:, The audit was funded by the Association of Paediatric Anaesthetists (APA) and performed by the acute pain services of 18 centers throughout the United Kingdom. Data were submitted weekly via a web-based return form designed by the Document Capture Company that documented data on all patients receiving opioid infusions and any SCIs. Eight categories of SCI were identified in advance, and the reported SCIs were graded in terms of severity (Grade 1 (death/permanent harm); Grade 2 (harm but full recovery and resulting in termination of the technique or needing significant intervention); Grade 3 (potential but no actual harm). Data were collected over a period of 17 months (25/06/07-25/11/08) and stored on a secure server for analysis. Results:, Forty-six SCIs were reported in 10 726 opioid infusion techniques. One Grade 1 incident (1 : 10 726) of cardiac arrest occurred and was associated with aspiration pneumonitis and the underlying neurological condition, neurocutaneous melanosis. Twenty-eight Grade 2 incidents (1 : 383) were reported of which half were respiratory depression. The seventeen Grade 3 incidents (1 : 631) were all drug errors because of programming or prescribing errors and were all reported by one center. Conclusions:, The overall incidence of 1 : 10 000 of serious harm with opioid infusion techniques in children is comparable to the risks with pediatric epidural infusions and central blocks identified by two recent UK national audits (1,2). Avoidable factors were identified including prescription and pump programming errors, use of concurrent sedatives or opioids by different routes and overgenerous dosing in infants. Early respiratory depression in patients with specific risk factors, such as young age, neurodevelopmental, respiratory, or cardiac comorbidities, who are receiving nurse-controlled analgesia or continuous opioid infusion suggests that closer monitoring for at least 2 h is needed for these cases. As a result of this audit, we can provide parents with better information on relative risks to help the process of informed consent. [source]

Prolonged apnea with intramuscular ketamine: a case report

PEDIATRIC ANESTHESIA, Issue 4 2008
NIRMALA JONNAVITHULA MD
Summary We report a rare case of prolonged apnea following administration of ketamine. A healthy 11-month-old female child was administered intramuscular ketamine as a sole anesthetic agent for a short surgical procedure. Child developed respiratory depression and prolonged apnea requiring intubation and ventilation. She recovered completely after 90 min. This case report illustrates the potential hazard of ketamine, emphasizes the importance of being able to provide emergency airway management and monitored anesthesia care. [source]

Continuous venovenous hemodiafiltration to treat controlled-release carbamazepine overdose in a pediatric patient

PEDIATRIC ANESTHESIA, Issue 11 2006
TULAY SAHIN YILDIZ MD
Summary Carbamazepine (CBZ) intoxication is an important issue in acute poisoning practice. Highly protein-bound, CBZ is not removed efficiently through conventional hemodialysis. We describe the use of continuous venovenous hemodiafiltration (CVVHDF) in a 2-year-old boy who developed general tonic clonic seizure and respiratory depression due to controlled-release formula of CBZ overdose (peak drug level of >20 ,g·ml,1, therapeutic range: 5,10 ,g·ml,1). Serum CBZ concentrations fell to 0.25 ,g·ml,1 at the end of hemodiafiltration. The patient recovered rapidly and was discharged from hospital 4 days from the time of ingestion with no complications or neurologic impairment. [source]

Tramadol for pain relief in children undergoing herniotomy: a comparison with ilioinguinal and iliohypogastric blocks

PEDIATRIC ANESTHESIA, Issue 1 2006
MOHAMMAD BAGHER KHOSRAVI MD
Summary Background:, Prevention of postoperative pain in children is one of the most important objectives of the anesthesiologist. Preoperative ilioinguinal and iliohypogastric nerve blocks have been widely used to provide analgesia in children undergoing herniorrhaphy. Tramadol is an analgesic with micro-opioid and nonopioid activity. In this study we compared the usage of intravenous tramadol with ilioinguinal and iliohypogastric nerve blocks for control of postherniorrhaphy pain in children aged 2,7 years. Methods:, Sixty patients were randomly allocated to two groups of thirty. One group received tramadol 1.5 mg·kg,1 i.v. before induction of general anesthesia and the other had an ilioinguinal and iliohypogastric nerve block with 0.5% bupivacaine (0.25 ml·kg,1) before skin incision. We assessed pain using the Children's Hospital of Eastern Ontario Pain Scale and the Categorical Pain Scale. Results:, At 1, 4 and 24 h after surgery the two groups had identical pain scores. At 2 and 3 h after surgery the tramadol group experienced significantly less pain (P < 0.05). The rescue drug for residual pain, was used equally in the two groups. None of the 60 patients had respiratory depression but the tramadol group patients were found to have more episodes of nausea and vomiting (P < 0.05). Conclusions:, We concluded that tramadol can have at least the same analgesic effect as that of ilioinguinal and iliohypogastric nerve blocks for postherniorrhaphy pain in children, with even a superior effect at the time of maximal analgesia. We also highlight the troublesome side-effect of nausea and vomiting which brings into question the benefits of using this opioid that seems to lack respiratory depression. [source]

Use of intravenous ketorolac in the neonate and premature babies

PEDIATRIC ANESTHESIA, Issue 6 2004
Patrizia Papacci MD
Summary Background :,Ketorolac is a powerful nonsteroidal anti-inflammatory drug widely used for pain control in children and adults. The aim of this study was to evaluate its safety and analgesic efficacy in the neonate. Methods :,Ketorolac was used in a group of 18 spontaneously breathing neonates presenting with chronic lung disease, for the control of postsurgical pain and pain from invasive procedures. Pain scores (Neonatal Infant Pain Scale) were assessed before and after i.v. administration of 1 mg·kg,1 of ketorolac. Results :,Total pain control was achieved in 94.4% of the neonates. None of the neonates had haematological, renal or hepatic changes prior to treatment, and these complications did not occur after treatment. No neonate had systemic haemorrhage or bleeding from injection and blood withdrawal sites. Conclusions :,Ketorolac could represent an efficacious analgesic alternative to opioids, particularly in neonates. It would avoid the side-effects associated with opioid analgesics, especially respiratory depression. [source]

Tramadol for pain relief in children undergoing tonsillectomy: a comparison with morphine

PEDIATRIC ANESTHESIA, Issue 3 2003
Thomas Engelhardt MD
SummaryBackground: Pain control for paediatric patients undergoing tonsillectomy remains problematic. Tramadol is reported to be an effective analgesic and to have a side-effect profile similar to morphine, but is currently not licensed for paediatric use in the UK. Methods: We conducted a prospective, double-blind, randomized controlled trial in children who were scheduled for elective tonsillectomy or adenotonsillectomy at the Royal Aberdeen Children Hospital. Following local ethics committee approval and after obtaining a drug exemption certificate from the Medicines Licensing Agency for an unlicensed drug, we recruited 20 patients each into morphine (0.1 mg·kg,1), tramadol (1 mg·kg,1) and tramadol (2 mg·kg,1) groups. These drugs were given as a single injection following induction of anaesthesia. In addition, all patients received diclofenac (1 mg·kg,1) rectally. The postoperative pain scores, analgesic requirements, sedation scores, signs of respiratory depression and nausea and vomiting, as well as antiemetic requirements, were noted at 4-h intervals until discharge. Results: There were no statistically significant differences in age, weight, type of operation or induction of anaesthesia, 4-h sedation and pain scores and further analgesic requirements. There were no episodes of respiratory depression. Morphine was associated with a significantly higher incidence of vomiting following discharge to the wards (75% versus 40%, P=0.03) compared with both tramadol groups. Conclusions: Tramadol has similar analgesic properties, when compared with morphine. The various pharmaceutical presentations and the availability as a noncontrolled substance may make it a useful addition to paediatric anaesthesia if it becomes licensed for paediatric anaesthesia in the UK. [source]

Analgesic studies on total alkaloids and alcohol extracts of Eclipta alba (Linn.) Hassk.

PHYTOTHERAPY RESEARCH, Issue 2 2004
Mahesh Sawant
Abstract A variety of analgesics are used for the treatment of acute and chronic pain in different disease states. A narcotic or a non-narcotic analgesic that does not cause respiratory depression and addiction is needed. In Ayurveda a large number of indigenous drugs have been mentioned possessing analgesic properties (e.g. Guggul, Erand, Rasna, Bhringaraj, Methika, Palandu and Prasikayavani). The present experimental research work was undertaken to determine the analgesic activity of the total ethanol extract of Eclipta alba, and also the isolated alkaloids of Eclipta alba in albino mice by using standard experimental models such as the tail clip method, the tail ,ick method and the acetic acid induced writhing response. The results from this study show that both the ethanol extract as well as the total alkaloids produce good analgesic activity in all the different models of analgesia used. The total alkaloidal fraction was the most ef,cacious in all models tested. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Co-worker fatalities from hydrogen sulfide

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2004
Robert G. Hendrickson MD
Abstract Background Hydrogen sulfide is a colorless, odorless gas that may cause rapid loss of consciousness and respiratory depression without warning. It has produced toxicity in workers in numerous industries and occupations. Methods A review of the United States Bureau of Labor Statistics (USBLS) Census of Fatal Occupational Injuries (CFOI) for occupational deaths related to hydrogen sulfide from 1993 to 1999 was performed. Results Fifty-two workers died of hydrogen sulfide toxicity in this 7-year period. Deaths were most commonly reported in workers who were white (85%), male (98%), and in their first year of employment with the company (48%). Common industries included waste management, petroleum, and natural gas. In 21% of cases, a co-worker died simultaneously or in the attempt to save the workers. Conclusions Hydrogen sulfide toxicity is uncommon, but potentially deadly. Toxicity is predominantly in new workers and co-worker fatalities occur in a significant minority of cases. Proper training and education on the warning signs of hydrogen sulfide toxicity may help reduce worker fatalities. Am. J. Ind. Med. 45:346,350, 2004. © 2004 Wiley-Liss, Inc. [source]

Hypoxia-sensing properties of the newborn rat ventral medullary surface in vitro

THE JOURNAL OF PHYSIOLOGY, Issue 1 2006
N. Voituron
The ventral medullary surface (VMS) is a region known to exert a respiratory stimulant effect during hypercapnia. Several studies have suggested its involvement in the central inhibition of respiratory rhythm caused by hypoxia. We studied brainstem,spinal cord preparations isolated from newborn rats transiently superfused with a very low O2 medium, causing reversible respiratory depression, to characterize the participation of the VMS in hypoxic respiratory adaptation. In the presence of 0.8 mm Ca2+, very low O2 medium induced an increase in c-fos expression throughout the VMS. The reduction of synaptic transmission and blockade of the respiratory drive by 0.2 mm Ca2+,1.6 mm Mg2+ abolished c-fos expression in the medial VMS (at the lateral edge of the pyramidal tract) but not in the perifacial retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) VMS, suggesting the existence of perifacial RTN/pFRG hypoxia-sensing neurons. In the presence of Ca2+ (0.8 mm), lesioning experiments suggested a physiological difference in perifacial RTN/pFRG VMS between the lateral VMS (beneath the ventrolateral part of the facial nucleus) and the middle VMS (beneath the ventromedial part of the facial nucleus), at least in newborn rats. The lateral VMS lesion, corresponding principally to the most rostral part of the pFRG, produced hypoxia-induced stimulation, whereas the middle VMS lesion, corresponding to the main part of the RTN, abolished hypoxic excitation. This may involve relay via the medial VMS, which is thought to be the parapyramidal group. [source]

A comparison of the respiratory effects of oxycodone versus morphine: a randomised, double-blind, placebo-controlled investigation,

ANAESTHESIA, Issue 10 2010
S. H. Chang
Summary Oxycodone's respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri-operative period. We randomly assigned ASA 1-2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg,1, or oxycodone 0.05 mg.kg,1, 0.1 mg.kg,1, or 0.2 mg.kg,1. Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg,1, oxycodone 0.05 mg.kg,1 and 0.1 mg.kg,1, and from 10 patients who received oxycodone 0.2 mg.kg,1. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p < 0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine. [source]