Electromyographic signal-activated functional electrical stimulation of abdominal muscles: the effect on pulmonary function in patients with tetraplegia.

BACKGROUND: Paralysis of abdominal muscles is the main cause of respiratory dysfunctions in patients with lower cervical spinal cord lesion. Activation of the abdominal muscles using functional electrical stimulation (FES) improved respiratory function in these patients. But application of FES frequently requires a caregiver, and it may not be well synchronized with the patient's respiratory activity. OBJECTIVE: To perform preliminary examination of electromyographic (EMG)-activated FES for caregiver-independent and synchronized cough and expiration induction in tetraplegia. DESIGN: Self-controlled study. SETTING: Loewenstein Rehabilitation Center, Raanana, Israel. SUBJECTS: A total of 10 male patients with complete or almost complete tetraplegia. MAIN OUTCOME MEASURES: Peak expiratory flow (PEF), forced vital capacity (FVC), and maximal voluntary ventilation (MVV). METHODS: The outcome measures were examined with the abdominal muscles unassisted or assisted by various methods. These included manual assistance or application of FES, activated by a caregiver, by the patient, or by EMG signals elicited from the patient's muscle. RESULTS: Manual assistance improved the mean PEF value by 36.7% (P<0.01) and the mean FVC value by 15.4% (P=0.01). FES did not significantly change most measurements, and patient-activated FES even reduced PEF (P<0.05). But following EMG-activated FES PEF and FVC values were higher than those following patient-activated FES (P<0.05 for PEF; P<0.01 for FVC), and their mean values were higher by 15.8 and 18.9%, respectively. CONCLUSIONS: Abdominal FES failed to improve respiratory function in this study, but applying FES to abdominal muscles by EMG from the patient's muscle may promote caregiver-free respiration and coughing in persons with cervical SCL.

Mesenteric artery clamping/unclamping-induced acute lung injury is attenuated by N-methyl-D-aspartate antagonist dextromethorphan.

Lung N-methyl-D-aspartate receptors (NMDAR) may cause excitotoxic pulmonary edema if activated. Acute lung injury may be mediated by oxidative stress, frequently generated by local or remote ischemia and reperfusion (IR). This experimental study assessed the effects of intravenous dextromethorphan, an NMDAR antagonist, on reperfusion lung injury following superior mesenteric artery (SMA) clamping/unclamping. SMA of 48 (12 per group) anesthetized adult male Wistar rats was clamped for 90 min (IR); 48 additional rats underwent a sham laparotomy (control). The experimental timeframe was identical in all groups. Ten minutes before unclamping, three dextromethorphan doses were administered intravenously in three IR and three control groups, followed by 3 h of respiratory and hemodynamic assessment and postexperimental assessment of survival. Intravenous 10 and 20 mg/kg dextromethorphan attenuated an 85% increase in peak ventilatory pressure, a 45% reduction in PO(2)/FiO(2), 4-12-fold increase in bronchoalveolar lavage-retrieved volume, and polymorphonuclear leukocytes/bronchoalveolar cells ratio, all associated with SMA unclamping in the IR-nontreated and the IR-40 mg/kg dextromethorphan-treated rats. Lung tissue polymorphonuclear leukocyte count, total xanthine oxidase activity, reduced glutathione, and wet-to-dry weight ratio were all within normal ranges in the two lower-dose-treated groups. These effective regimens were also associated with longer postexperimental animal survival. Dextromethorphan was not associated with changes in three control groups. Thus, Intravenous dextromethorphan mitigates lung reperfusion injury following SMA clamping/unclamping in a dose-dependent manner. This is a novel potential use of dextromethorphan in vivo.

The assessment of radiating low back pain by thermal sensory testing.

Low back pain radiating into the legs is a common pain syndrome. However, neurological examination, imaging and electromyographic studies are of limited value for prognosis or therapy. The origin of the pain remains unknown. The aim was to evaluate the potential of thermal sensory testing to serve as a diagnostic tool in 24 patients who had low back pain radiating down the S1 dermatome, compared with 26 pain-free controls. The method of limits was used to detect the thresholds of warm sensation, cold sensation, warm pain and cold pain at the L4, L5 and S1 dermatomes of the symptomatic and the non-symptomatic legs. Thresholds on the asymptomatic leg were similar to values obtained in controls. We found a significantly higher threshold for cold sensation in the S1 dermatome of the symptomatic leg of the patients compared with the controls (p< 0.005). In addition, patients who had abnormal neurological examination (50%) had higher thresholds for cold sensation or cold pain in the three dermatomes tested at the symptomatic leg compared with the non-symptomatic leg. No differences in the thresholds of warm sensation or warm pain were detected. We propose that these findings indicate selective damage to the Adelta fibres which are involved in transmission of cold sensation and pain, presumably by root compression. We found no evidence of involvement of C fibres, which transmit warm sensation and pain. Thermal testing should be considered among the testing modalities that are capable of demonstrating objective findings in patients with radiating low back pain.

[The benefit of combining spinal morphine and intravenous buprenorphine for perioperative pain].

Concurrent administration of opioids with different affinity produces synergistic antinociceptive effect in rats. We tested the perioperative antinociceptive effects of the simultaneous double blind administration of morphine, a pure agonist and buprenorphine, a partial agonist, in 30 patients undergoing hysterectomy under general anesthesia. Pre- and post-operatively regimens consisted of random patient assignment to intrathecal 0.3 mg morphine plus intravenous saline (group 1), intravenous 0.09 mg buprenorphine plus intrathecal saline (group 2) or intrathecal morphine 0.3 mg plus intravenous buprenorphine 0.09 mg (group 3). Postoperative pain relief for group 3 consisted of supplementation of intravenous buprenorphine plus intrathecal saline. The immediate postoperative pain, sedation and anxiety levels (by numerical or categorical scores) were similar among all groups. The 12-hour pain and sedation scores were significantly (P < 0.05) lower in group 3 than in the other two groups. Buprenorphine-induced analgesia in group 3 lasted significantly (P < 0.05) longer than in group 2. Side effects in groups 2 and 3 were by 44% and 42% fewer than in group 1, respectively, with no withdrawal symptoms. Thus, concomitant administration of intrathecal morphine and low dose intravenous buprenorphine produces better and longer pain relief than intravenous buprenorphine alone in women after hysterectomy.

Combined pre-incisional oral dextromethorphan and epidural lidocaine for postoperative pain reduction and morphine sparing: a randomised double-blind study on day-surgery patients.

The reduction in acute pain perception following dextromethorphan has previously been investigated in patients undergoing general anaesthesia. This random and double-blind study examined the effects of pre-incisional oral dextromethorphan on postoperative pain and intravenous patient-controlled morphine demand in 60 day-surgery patients undergoing lower body surgery under lidocaine (1.6%-16 ml) epidural anaesthesia after receiving placebo, 60 or 90 mg dextromethorphan, 90 min pre-operatively. Postoperative pain was scored on a visual analogue scale from 1 to 10. In-hospital observation continued for 6 h and for 3 days at home; diclofenac was available throughout. Dextromethorphan-treated patients reported significantly (p < 0.05) less pain and sedation, and felt better. Patients who received dextromethorphan 90 mg had significantly (p < 0.05) lower heart and respiratory rates than those who received 60 mg. Medicated patients required half the morphine and diclofenac of placebo patients: 38% of patients who received 90 mg and 21% who received dextromethorphan 60 mg used no morphine or diclofenac whatsoever, a previously unreported finding.

Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia.

PURPOSE: To determine the effect of 90 mg dextromethorphan (DM) p.o. vs placebo 90 min preoperatively, on the immediate and delayed postoperative course. METHODS: Thirty patients undergoing laparoscopic cholecystectomy or inguinal hernioplasty under general anesthesia were studied. Half (DM) received 90 mg dextromethorphan and half received placebo 90 min before anesthesia. Intravenous Patient Controlled Aanalgesia with morphine was available for two hours within a six-hour observation period; 75 mg diclofenac i.m. prn was given later in PACU and on-ward (24 hr). Pain was assessed using the visual analogue scales. Thermal thresholds for cold and hot sensation and for pain (by limit method) were evaluated at the site of skin incision (primary-) and distantly (secondary hyperalgesia). Von Frey filaments were applied testing touch sensation. Sedation level and morphine consumption were also assessed in PACU. RESULTS: Demographic, surgical and perioperative parameters were similar; no untoward effects were encountered. Pain intensity and sedation were lower, and the feeling of well-being was greater, in the DM patients: one vs five (median), two vs five, five vs two, respectively, P <0.01 (90 min time-point). Thermal application revealed absence of primary and secondary hyperalgesia only in the DM patients; von Frey filaments induced similar pain sensation in both groups. Mean morphine/group, morphine/weight and diclofenac injection rates were approximately 55% lower in the DM group: 2.1 +/- 1.2 (SD) vs 4.7 +/- 2.3, 0.03 +/- 0.02 vs 0.07 +/- 0.03, 1.0 +/- 0.3 vs 2.4 +/- 0.2, respectively, P <0.01. CONCLUSIONS: Compared with placebo, DM enabled reduction of postoperative analgesics consumption, improved well-being, and reduced sedation, pain intensity and primary and secondary thermal hyperalgesia.

Pain and quality of life.

This paper deals with the impact of pain on quality of life (QOL). Two major factors have contributed to the enhanced importance of QOL in recent years: the increasing frequency of pain and the resources devoted to its treatment, and the growing theoretical insight that pain affects the person as a whole. QOL is defined as the person's evaluation of his or her well-being and functioning in different life domains. It is a subjective, phenomenological, multidimensional, dynamic, evaluative, and yet quantifiable, construct. Commonly used scales for its assessment (eg, WHOQOL, SF-36) are described. Studies show that pain affects most domains of QOL, primarily physical and emotional functioning. The effect depends on the extent, duration, acuteness, intensity, affectivity, and meaning of the pain as well as on the underlying disease and the individual's characteristics. QOL is sensitive also to the treatment of pain and treatment modalities, as shown particularly by studies on cancer pain. Pain reduction is not always attended by the expected improvement in QOL. Pain is not synonymous with poor QOL and constitutes only one important factor determining QOL. The main conclusions are that treatment of pain should be multidisciplinary, considering the impact of pain and the treatment on QOL and targetting also improvement of the affected domains of QOL.

Flumazenil potentiation of postoperative morphine analgesia.

OBJECTIVE: The goal of this study was to test the effect of concomitant administration of flumazenil (FL) and morphine (MO) on immediate postoperative analgesia and the MO requirement to control pain in human beings. DESIGN AND INTERVENTIONS: Thirty-six patients undergoing inguinal hernioplasty under lidocaine epidural anesthesia were enrolled in this double-blind, randomized, controlled study. On the first complaint of pain, either MO (2 mg) only or MO (2 mg) plus FL (0.2 mg) was administered. Additional doses of the same medications administered via a patient-controlled analgesia device with a 10-minute lockout period were available thereafter. The study continued for 2 hours after the loading doses of the medications were administered, with an additional 2-hour period of observation. RESULTS: Thirty-two patients completed the study. Both groups reached a similar satisfactory equianalgesic state (2 in a 0-10 visual analogue scale). The MO plus FL group consumed 9.5 +/- 1.1 mg of MO versus 14.1 +/- 1.1 mg of MO (p < 0.001) in the MO only group. The MO plus FL patients were subjectively (visual analogue scale) more comfortable and less sedated than the MO patients. "Fine" coordination (using an electronic maze) and "coarse" coordination (measured by transferring a pen from one hand to another as rapidly as possible with both arms placed inside an 80-cm metal frame) in the MO group were worse than in the MO plus FL group. End-tidal CO2 increased and blood pressure decreased in the MO group. There were few and insignificant side effects in the MO group. None of these patients required an MO antagonist, and recovery was prolonged in none. CONCLUSIONS: Flumazenil afforded lower MO consumption during the immediate postoperative period. Cognitive, hemodynamic, and respiratory functions were better after MO plus FL than after MO alone.

Antinociceptive effect induced by the combined administration of spinal morphine and systemic buprenorphine.

UNLABELLED: We evaluated the antinociceptive effect of combined spinal administration of morphine and systemic administration of buprenorphine. Experiments were performed on male Wistar rats. Nociception was measured using the tail immersion test. Buprenorphine was injected intraperitoneally (IP) and morphine was injected intrathecally (IT) via a catheter implanted in the subarachnoid space. Interaction of drugs was analyzed using a dose addition model. Both IT (1-5 microg) morphine and IP (50-500 microg/kg) buprenorphine increased the latencies of nociceptive responses in a dose-dependent manner. IT morphine (4 microg) and IP buprenorphine (100 microg/kg) produced 62.9+/-6.3 and 48.8+/-6.6 percent of the maximal possible effect (%MPE), respectively. The combined administration of 2 microg of IT morphine and 50 microg/kg IP buprenorphine produced a %MPE of 97.1+/-3.4. The analysis of drug interaction revealed that IT morphine interacted with IP buprenorphine in a supraadditive manner while producing a potent antinociceptive effect. IMPLICATIONS: The concurrent administration of spinal morphine and systemic buprenorphine produces an antinociceptive effect that is greater than what could have been predicted from individual dose-response curves. This mode of interaction allows maintenance at a significant level of analgesia with reduced doses of opioids, which minimizes the incidence of undesirable side effects.

Direct induction of acute lung and myocardial dysfunction by liver ischemia and reperfusion.

OBJECTIVES: To investigate whether liver ischemia and reperfusion (IR) directly affect functions of remote organs. BACKGROUND: Cardiovascular and respiratory dysfunction follows hemorrhage, spinal shock, or trauma as a result of no-flow-reflow phenomena. Hepatic IR induces remote organ damage probably by xanthine oxidase and oxygen species. MATERIALS AND METHODS: Isolated rat livers, lungs, and hearts were perfused with Krebs-Henseleit solutions. After stabilization, livers were either perfused or made ischemic. Then, livers and hearts or livers and lungs were reperfused in series, and the liver was disconnected and the second organ continued to perfuse with the accumulated effluents. MEASUREMENTS AND MAIN RESULTS: Ischemic and reperfused liver effluent contained high lactate dehydrogenase and uric acid concentrations compared with controls; xanthine oxidase increased 60 to 100 times. Ischemic and reperfused lung peak inspiratory pressure almost doubled; airway static compliance halved; myocardial contractility decreased to 70% of baseline; wet weight-to-dry weight ratios of lungs and livers increased. CONCLUSION: Ischemic and reperfused liver can directly induce myocardial and pulmonary dysfunction, presumably by oxidant-induced injury.

The use of DNA markers in the pre-clinical diagnosis of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP), an autosomal dominant inherited disease, confers a high risk of colon cancer. For presymptomatic diagnosis of FAP, we performed linkage studies in three unrelated Israeli families with FAP, using seven polymorphic systems around or at the APC locus on chromosome 5q. These systems are constituted of three DNA probes, recognizing four restriction fragment length polymorphism: C11p11, YN5.48 and pi227; three cytosine-adenine repeat markers: D5S318, D5S346 and MBC; and one intragenic polymorphism: APC-SspI. A meiotic recombination event was detected, apparently between the FAP gene and probe pi227. Based on the different analysis systems, we determined the haplotype at the APC locus in 11 at-risk individuals of the three families, six of whom were found to carry the disease-linked allele. Additionally, we identified a new FAP patient, in whom sigmoidoscopy showed the presence of adenomatous polyps throughout the colon.

Use of flumazenil in the treatment of drug overdose: a double-blind and open clinical study in 110 patients.

OBJECTIVES: To assess the efficacy, usefulness, safety, and dosages of flumazenil required when flumazenil is used in the diagnosis of benzodiazepine-induced coma (vs. other drug-induced coma), and to reverse or prevent the recurrence of unconsciousness. DESIGN: A two-phase study: a controlled, randomized, double-blind study followed by a prospective, open study. SETTING: An 800-bed, teaching, university-affiliated hospital. PATIENTS: Unconscious patients (n = 110) suspected of benzodiazepine overdose, graded 2 to 4 on the Matthew and Lawson coma scale, were treated with flumazenil, the specific benzodiazepine receptor antagonist. The first 31 patients were studied in a double-blind fashion, while the rest of the patients were given flumazenil according to an open protocol. INTERVENTIONS; All patients received supplemental oxygen; endotracheal intubation was performed, and synchronized intermittent mandatory ventilation was initiated whenever it was deemed necessary. A peripheral intravenous cannula was inserted, as were indwelling arterial and urinary bladder catheters. Blood pressure, electrocardiogram, respiratory rate, end-tidal CO2, and core temperature were continuously monitored. The first 31 double-blind patients received either intravenous flumazenil (to a maximum of 1 mg) or saline, while the rest of the patients were given flumazenil until either regaining consciousness or a maximum of 2.5 mg was injected. Patients remaining unconscious among double-blind patients or those patients relapsing into coma after the first dose were later treated in the open phase of the study. Treatment continued by boluses or infusion as long as efficacious. MEASUREMENTS AND MAIN RESULTS: Fourteen of 17 double-blind, flumazenil-treated patients woke after a mean of 0.8 +/- 0.3 (SD) mg vs. one of 14 placebo patients (p < .001). Seventy-five percent of the aggregated controlled and uncontrolled patients awoke from coma scores of 3.1 +/- 0.6 to 0.4 +/- 0.5 (p < .01) after the injection of 0.7 +/- 0.3 mg of flumazenil. These patients had high benzodiazepine serum blood concentrations. Twenty-five percent of the patients did not regain consciousness. These patients had very high serum concentrations of nonbenzodiazepine drugs. Sixty percent of the responders who had primarily ingested benzodiazepines remained awake for 72 +/- 37 mins after flumazenil administration; 40% relapsed into coma after 18 +/- 7 mins and various central nervous system depressant drugs were detected in their blood in addition to benzodiazepines. Seventy-one percent of the patients had ingested tricyclic antidepressants. Seventy-eight percent of the responders were continually and efficaciously treated for < or = 8 days. Fourteen (25%) of the intubated patients were extubated safely while 12 patients, who had shown increased respiratory insufficiency, resumed satisfactory respiration after flumazenil injection. Five cases of transient increase in blood pressure and heart rate were encountered. There were 27 mildly unpleasant "waking" episodes, such as anxiety, restlessness, and aggression, but no patient had benzodiazepine withdrawal signs, convulsions, or dysrhythmia, most noticeably absent in tricyclic antidepressant-intoxicated patients. CONCLUSIONS: Flumazenil is a valid diagnostic tool for distinguishing pure benzodiazepine from mixed-drug intoxication or nondrug-induced coma. Flumazenil is effective in preventing recurrence of benzodiazepine-induced coma. Respiratory insufficiency is reversed after its administration. Flumazenil is safe when administered cautiously, even in patients with coma caused by a mixed overdose of benzodiazepine plus tricyclic antidepressants.

Effect of second-stage 0.25% epidural bupivacaine on the outcome of labor.

OBJECTIVE: To evaluate the effect of second-stage epidural bupivacaine on the outcome of labor. METHODS: Two groups of 35 patients each were randomly allocated to receive continuous epidural bupivacaine throughout labor (group 1) or until an 8-cm dilatation of the cervix (group 2). RESULTS: There was no significant difference between the 2 groups in the rates of instrument deliveries and in their Apgar scores. CONCLUSIONS: The administration of continuous epidural bupivacaine (0.25%) throughout labor and delivery does not seem to affect the outcome of labor.

Antinociception induced by simultaneous intrathecal and intraperitoneal administration of low doses of morphine.

The application of morphine simultaneously into the spinal cord and brain ventricles produces a supraadditive antinociceptive effect. In this study, we attempted to determine whether combined intrathecal (IT) and intraperitoneal (IP) administration of small doses of morphine also produces such a synergistic antinociceptive effect. The experiments were performed on male Wistar rats. Nociception was measured using the tail immersion test. For IT administration morphine was injected through a catheter implanted in the subarachnoid space. Combined administration of small doses of IT (1 microgram) and IP (1 mg/kg) morphine resulted in a strong, highly significant antinociceptive effect. This effect was not only much higher than that produced by separate administration of the same doses of morphine, but also much higher than the expected effect of the combination. These results demonstrate that low doses of IT and IP morphine interact in a supraadditive fashion to produce potent analgesia.

Localized fibromyalgia in a child.

A 14-year-old male was investigated because of a limp and a localized sharp pain in the right lumber paravertebral region radiating to the lower abdomen and the medial aspect of the thigh, which started following forced physical activity. With the diagnosis of fibromyalgia the patient received two perifacetal injections of local anaesthetics with steroids followed by transcutaneous electrical nerve stimulation (TENS). Following the injections, pain intensity dropped dramatically, disability was reduced and muscle swelling resolved. The possible association of symptoms to sport activity raises the question of sport-induced fibromyalgia, and the excellent response to treatment may suggest a facet joint irritation as possible aetiology.

Epidural morphine pretreatment for postepisiotomy pain.

OBJECTIVE/DESIGN: A randomized double-blind controlled study was conducted on two groups of 45 parturients to evaluate the importance of the timing of epidural morphine administration for the relief of postepisiotomy pain. Both groups had preemptive analgesia by continuous lumbar epidural bupivacaine blockade. Upon completion of the episiotomy repair and before the onset of pain, the patients received epidural injections of 3 ml saline with or without 2 mg morphine in groups A and B respectively. When pain appeared, group A patients received an epidural injection of 3 ml saline while group B patients received 2 mg morphine in 3 ml saline. Postepisiotomy pain level was evaluated by a visual analogue scale. RESULTS: The incidence of pain in group B women following epidural morphine administration was 68.6%. This was significantly higher than that of group A at 15.6% (p < 0.01). Furthermore, group B showed that the rate of effective pain relief after 2 mg epidural morphine significantly decreases as the level of pain intensity rises (p < 0.01). CONCLUSION: Epidural morphine for postepisiotomy pain is much more effective if administered before the onset of pain.