Am J Emerg Med 2001 Oct;19(6):492-4
Department of Emergency Medicine, Brooke Army Medical Center/San Antonio Uniformed Services Health Education Consortium, San Antonio, TX 78234, USA. robert.gerhardt@cen.amedd.army.mil
The objective was to determine whether an inhaled 50:50 mixture of nitrous oxide and oxygen (N(2)O/O(2)) provides significant pain and anxiety relief during intravenous cannulation in healthy adults. The study was conducted at the ED of a military teaching hospital. Participants included adult volunteers aged 18 to 50 years. Excluded were those with allergy to N(2)O, anemia, cardiac disease, pregnancy, asthma, or bone marrow disorder. A prospective, randomized, double-blind, placebo-controlled crossover design was used comparing a 50:50 mixture of N(2)O/O(2) versus O(2). After recording baseline nonhatched 100mm visual analog scales (VAS) for pain and anxiety, subjects inhaled gas 1 for 120 seconds, followed by antecubital intravenous cannulation, discontinuance of gas and VAS rating of procedural pain and anxiety. After 15 minutes, the experiment was repeated with gas 2. Ten subjects would detect a 12mm difference in pain or anxiety with a standard deviation of 10 mm, an alpha error under 0.05 and a power over 80%. Differences between VAS were compared by matched 2-tailed t-test. Eleven subjects were enrolled. One withdrew because of dizziness while inhaling gas (N(2)O). The 10 remaining subjects reported significantly less pain (N(2)O/O(2) 14.5mm, SD 18; O(2) 34.3mm, SD 23.4; P < .01) and anxiety (N(2)O/O(2) - 7.9mm, SD 7.8; O(2) 6.0mm, SD 11.6; P < .02) when inhaling N(2)O/O(2) than when inhaling O(2) alone. N(2)O/O(2) provided significant pain and anxiety reductions during intravenous cannulation. Some patients may experience adverse perceptions while using N(2)O, limiting its utility. Further studies defining the role of N(2)O as an anxiolytic agent, efficacy in actual patients, and cost comparisons with intravenous conscious analgesia/sedation, are warranted.
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PMID: 11593469, UI: 21476781
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Anesth Analg 2001 Nov;93(5):1321-6
Department of Anesthesiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 021115, USA. chundhar_@hotmail.com
In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3-15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5-15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10-48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4-36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures. IMPLICATIONS: Ketamine added to epidural morphine given before surgery can decrease postoperative pain by its preemptive effect, opioid potentiation, and prevention of acute opioid tolerance. A single epidural bolus of 1 mg/kg of ketamine with morphine given before major upper-abdominal surgery did not result in a clinically relevant reduction in postoperative pain relief.
PMID: 11682423, UI: 21538418
Anesth Analg 2001 Nov;93(5):1310-5
Division of Pain Medicine, Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
We sought to determine whether tizanidine, an alpha2-agonist, relieved thermal hyperalgesia in rats with surgically induced neuropathic pain. We used a Sprague-Dawley rat model in which a chronic constriction of the sciatic nerve caused the rats to develop postural changes, mechanical allodynia, and thermal hyperalgesia. Thermal hyperalgesia was verified through paw withdrawal latency (PWL). PWL was tested before surgery, after surgery, and after injections with tizanidine (0.5, 1.0, or 2.0 mg/kg) or normal saline. Ambulatory and total movements were evaluated by placing the rats in activity cages. Thermal hyperalgesia was induced in all rats after surgery. Tizanidine, but not saline, caused a significant improvement in PWL (P < 0.05), with complete reversal of thermal hyperalgesia at all doses on postoperative Day 6. Rats who received tizanidine 2 mg/kg maintained complete reversal of thermal hyperalgesia through postoperative Day 9. Some sedation was observed with tizanidine 2 mg/kg, but not with smaller doses. We conclude that tizanidine effectively reversed thermal hyperalgesia in a rat model. IMPLICATIONS: This study was conducted to determine whether tizanidine could attenuate the thermal hyperalgesia that occurs in rats with surgically induced chronic constriction of the sciatic nerve. Tizanidine was effective in reducing sensitivity to heat, as measured by paw withdrawal latency, and did not cause sedation at smaller doses.
PMID: 11682421, UI: 21538416
Anesth Analg 2001 Nov;93(5):1297-303
Department of Anesthesiology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea. jhhwang@amc.seoul.kr
Nerve ligation injury may produce a pain syndrome that includes tactile allodynia. Reversal effects on tactile allodynia have been demonstrated after the intrathecal administration of gamma-aminobutyric acid (GABA) receptor agonists or cholinesterase inhibitors in rats. We examined the drug interactions between neostigmine and muscimol or baclofen in a rat model of nerve ligation injury. Rats were prepared with tight ligation of the left L5-6 spinal nerves and chronic intrathecal catheter implantation. Tactile allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hindpaw. Thresholds for paw withdrawal were assessed. Neostigmine (0.3-10 microg), muscimol (0.1-10 microg), and baclofen (0.1-3.0 microg) were administered to obtain the dose-response curve and the 50% effective dose (ED(50)). Fractions of ED(50) values were administered intrathecally to establish the ED(50)s of drug combinations (neostigmine-muscimol and neostigmine-baclofen). The drug interactions were performed. Intrathecal neostigmine, muscimol, baclofen, and their combinations produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination was additive. These results suggest that the activation of both muscarinic and GABA(A) receptors is required for synergistic interaction. IMPLICATIONS: This study indicates that drug interaction is synergistic for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination is additive. In a rat model of nerve ligation injury, neostigmine, muscimol, baclofen, and their combinations provide an antagonism on touch-evoked allodynia at the spinal level.
PMID: 11682418, UI: 21538413
Anesthesiology 2001 Nov;95(5):1198-204
Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. mujtaba@zeus.bwh.harvard.edu
BACKGROUND: Local anesthetics that produce analgesia of long duration with minimal impairment of autonomic functions are highly desirable for pain management in the clinic. Prenylamine is a known calcium channel blocker, but its local anesthetic blocking effects on voltage-gated sodium channels have not been studied thus far. METHODS: The authors characterized the tonic and use-dependent prenylamine block of native Na(+) channels in cultured rat neuronal GH3 cells during whole cell voltage clamp conditions and the local anesthetic effect of prenylamine by neurologic evaluation of sensory and motor functions of sciatic nerve during neural block in rats. RESULTS: Prenylamine elicits both use-dependent block of Na(+) channels during repetitive pulses (3 microm prenylamine produced 50% block at 5 Hz) and tonic block for both resting and inactivated Na(+) channels. The 50% inhibitory concentration for prenylamine was 27.6 +/- 1.3 microm for resting channels and 0.75 +/- 0.02 microm for inactivated channels. Furthermore, in vivo data show that 10 mm prenylamine produced a complete sciatic nerve block of motor function, proprioceptive responses, and nociceptive responses that lasted approximately 27, 34, and 24 h, respectively. Rats injected with 15.4 mm bupivacaine, a known local anesthetic currently used for pain management, had a significantly shorter duration of blockade (< 2 h) compared with rats injected with prenylamine. CONCLUSIONS: The data presented here demonstrate that prenylamine possesses local anesthetic properties in vitro and elicits prolonged local anesthesia in vivo.
PMID: 11684990, UI: 21540544
Anesthesiology 2001 Nov;95(5):1054-67
Department of Anesthesia and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-8711, USA. enorris@jhmi.edu
BACKGROUND: Improvement in patient outcome and reduced use of medical resources may result from using epidural anesthesia and analgesia as compared with general anesthesia and intravenous opioids, although the relative importance of intraoperative versus postoperative technique has not been studied. This prospective, double-masked, randomized clinical trial was designed to compare alternate combinations of intraoperative anesthesia and postoperative analgesia with respect to postoperative outcomes in patients undergoing surgery of the abdominal aorta. METHODS: One hundred sixty-eight patients undergoing surgery of the abdominal aorta were randomly assigned to receive either thoracic epidural anesthesia combined with a light general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural patient-controlled analgesia postoperatively (four treatment groups). Patient-controlled analgesia was continued for at least 72 h. Protocols were used to standardize perioperative medical management and to preserve masking intraoperatively and postoperatively. A uniform surveillance strategy was used for the identification of prospectively defined postoperative complications. Outcome evaluation included postoperative hospital length of stay, direct medical costs, selected postoperative morbidities, and postoperative recovery milestones. RESULTS: Length of stay and direct medical costs for patients surviving to discharge were similar among the four treatment groups. Postoperative outcomes were similar among the four treatment groups with respect to death, myocardial infarction, myocardial ischemia, reoperation, pneumonia, and renal failure. Epidural patient-controlled analgesia was associated with a significantly shorter time to extubation (P = 0.002). Times to intensive care unit discharge, ward admission, first bowel sounds, first flatus, tolerating clear liquids, tolerating regular diet, and independent ambulation were similar among the four treatment groups. Postoperative pain scores were also similar among the four treatment groups. CONCLUSIONS: In patients undergoing surgery of the abdominal aorta, thoracic epidural anesthesia combined with a light general anesthesia and followed by either intravenous or epidural patient-controlled analgesia, offers no major advantage or disadvantage when compared with general anesthesia alone followed by either intravenous or epidural patient-controlled analgesia.
PMID: 11684971, UI: 21540525
BMJ 2001 Nov 10;323(7321):1123-4
Integrative Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA. vickersa@mskcc.org
PMID: 11701584, UI: 21558010
Br J Anaesth 2001 May;86(5):720-3
Department of Anaesthetics, St Thomas' Hospital, London, UK.
Subdural haematoma is a well-documented complication of accidental dural puncture, and is thought to be preventable by prompt treatment with an epidural blood patch. An accidental dural puncture occurred in a 39-yr-old primagravida during the siting of an epidural catheter for pain relief in labour. Twenty hours after the puncture, the mother developed a typical postdural puncture headache, which increased in severity over the subsequent 24 h. An epidural blood patch was performed at 48 h, and this initially relieved the headache. After discharge from hospital, and 14 days after the dural puncture, the headache recurred, together with expressive dysphasia, poor co-ordination and sensory loss in the right arm. A magnetic resonance imaging scan demonstrated a left sided subdural haematoma, which was drained successfully with complete recovery.
PMID: 11575351, UI: 21459193
Eur J Anaesthesiol 2001 Nov;18(11):745-54
Department of Anaesthesia, Our Lady's Hospital for Sick Children, Dublin, Ireland.
BACKGROUND AND OBJECTIVE: Epidermolysis bullosa is a rare, genetically determined disorder characterized by excessive susceptibility of the skin and mucosa to separate from the underlying tissues after mechanical trauma. Patients suffering from this disease may have multiple medical problems, but the risk of anaesthesia is attributed mainly to oropharyngeal involvement; airway management may be hazardous and preservation of mucosa and skin integrity problematical. There is a paucity of data in the literature concerning the perioperative management of children with epidermolysis bullosa. We present our experience of managing 54 general anaesthetics (and two local anaesthetics) over the past 20 years. METHODS: The case notes of 16 children with epidermolysis bullosa were reviewed. The children underwent surgical procedures under local or general anaesthesia over a 20-year period. RESULTS: Fifty-four general and two local anaesthetics were administered for 58 procedures in 10 children (mean age 12.6 years). Surgical procedures included oesophageal dilatation (24), insertion/revision of gastrostomy (16), dental procedures (10), hand surgery (2), skin biopsy (2) and others (4). Anaesthesia was induced by inhalation in 73.4% of patients and the airway was maintained with an endotracheal tube in 64.8%. Monitoring of anaesthesia was performed with pulse oximetry (89%), whereas electrocardiography and non-invasive blood pressure monitoring were used in 16.6% of cases each. The mean duration of anaesthesia was 64 min. Tracheal intubation was difficult in two of the five children who were intubated. Mucocutaneous blistering occurred in three children, otherwise there was no attributable morbidity. CONCLUSION: With maximal skin and mucous membrane protection, anaesthesia in children with epidermolysis bullosa may be undertaken with few sequelae.
PMID: 11580781, UI: 21464615
Eur J Anaesthesiol 2001 Oct;18(10):695-6
Cukurova University Faculty of Medicine, Department of Anaesthesiology, Adana, Turkey.
PMID: 11553247, UI: 21437516
Eur J Anaesthesiol 2001 Oct;18(10):679-86
Department of Anaesthesiology and Intensive Care, Kristianstad Central Hospital, Kristianstad, Sweden.
BACKGROUND AND OBJECTIVE: Hypothermia may alter the disposition of opioids. Because opioids are commonly used as analgesics in the postoperative period, it is of clinical interest to clarify whether perioperatively developed hypothermia affects postoperative opioid requirements. METHODS: Fifty-nine patients undergoing subtotal hysterectomy were prospectively randomized and either treated intraoperatively with forced air warming, or served as controls covered with conventional blankets without active warming. Both groups received postoperative patient-controlled analgesia with the opioid ketobemidone. Total analgesic requirements, demands, analgesic requirements over 6-h intervals and pain scores were measured for 48 h. Core temperature at the tympanic membrane and ambient room temperature were measured during the perioperative period. RESULTS: There were no postoperative differences in analgesic requirements or pain intensity between normothermic and hypothermic patients. Patients treated with warm air had an up to 1 degree C higher core temperature from 0.5 h after anaesthesia induction until almost 2 h postoperatively. The actively warmed patients also had a lower intraoperative blood loss than the hypothermic patients (186 +/- 27 mL vs. 308 +/- 47 mL; P < 0.05). CONCLUSION: In a clinical setting, opioid requirements do not seem to be affected by mild postoperative hypothermia after lower abdominal surgery.
PMID: 11553245, UI: 21437514
Eur J Pharmacol 2001 Jul 27;424(3):195-8
2nd Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ohmefentanyl is a very potent and highly selective agonist for mu-opioid receptors. We now study analgesia, in vitro activity and opioid receptor affinity of the stereoisomers of ohmefentanyl isothiocyanate. We found that some isomers of ohmefentanyl isothiocyanate had a potent analgesic effect and that all isomers except (3R,4S,2'S)-ohmefentanyl isothiocyanate had a more potent inhibitory action on the electrically evoked contractions of mouse vas deferens than of guinea pig ileum. The inhibitory actions could be antagonized by naloxone. However, compared with the activity of the corresponding stereoisomers of ohmefentanyl, these ohmefentanyl isothiocyanates had significantly reduced analgesia and in vitro activity. They also inhibited the binding of [3H]DPDPE ([D-Pen(2),D-Pen(5)]enkephalin) and [3H]DAGO ([D-Ala(2),Mephe(4),Gly-ol(5)]enkephalin) to opioid receptors in mouse brain membranes. The inhibitory effect of stereoisomers of ohmefentanyl isothiocyanate at mu-opioid receptors was markedly lower than that of their parent compounds. The affinity of stereoisomers of ohmefentanyl isothiocyanate for delta-opioid receptors was, however, greater than or equal to that of their corresponding stereoisomers of ohmefentanyl. The results showed that the introduction of an isothiocyanato group into the phenyl ring in position-1 of ohmefentanyl reduced bioactivity and affinity to mu-opioid receptors but that the selectivity of these compounds for delta-opioid receptors was enhanced. Isomer (3R,4S,2'R)-ohmefentanyl isothiocyanate showed highest selectivity for delta-opioid receptors (K(i)(mu)/K(i)(delta)=13.6) and potent analgesic activity (ED(50)=0.25 mg/kg).
PMID: 11672562, UI: 21526860
Lancet 2001 Nov 3;358(9292):1548
PMID: 11705595, UI: 21562895
Pediatrics 2001 Nov;108(5):1233-4
PMID: 11700639, UI: 21557369
PMID: 11694711, UI: 21551662
Pediatrics 2001 Oct;108(4):1047-8
PMID: 11589211, UI: 21471607
Support Care Cancer 2001 Jun;9(4):213-22
Division de Pharmacologie Clinique, Centre Hospitalier Universitaire, Vaudois, Lausanne, Switzerland.
Besides benzodiazepine, antidepressant and neuroleptic agents, all of which have established roles in supportive care, other psychotropic drugs deserve consideration in selected conditions affecting patients with advanced cancer. This article briefly reviews relevant aspects of miscellaneous psychotropics available for secondline treatment, including nonbenzodiazepine sedative, hypnotic and anxiolytic drugs, anaesthetic agents, stimulants, and analgesic adjuvants acting on the central nervous system. The proper use of such subsidiary psychotropic agents requires that both their specificities and the particular characteristics of palliative care patients are taken into account.
PMID: 11430416, UI: 21323125
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