Buprenorphine in opiate withdrawal: a comparison with clonidine

Clinical efficacy of buprenorphine in controlling withdrawal symptoms was compared against clonidine among 44 opiate dependent males. Subjective and objective withdrawal symptoms were assessed by withdrawal rating scales daily for 10 days. The subjects were randomly assigned to fixed dose schedule of either buprenorphine (0.6-1.2 mg per day, sublingually) or clonidine (0.3-0.9 mg per day, oral) for 10 days. Buprenorphine was found superior to clonidine in alleviating most of the subjective and objective opiate withdrawal symptoms. Subjective symptoms declined earlier among the subjects receiving buprenorphine. No untoward side-effects of buprenorphine were noticed.     

Effects of oral clonidine premedication on plasma glucose and lipid homeostasis associated with exogenous glucose infusion in children

BACKGROUND: Oral clonidine may influence plasma glucose and lipid homeostasis by modulating endocrinologic responses to surgical stress. The effect of oral clonidine premedication on plasma glucose and lipid homeostasis associated with exogenous glucose infusion were investigated in children undergoing minor surgery. METHODS: Otherwise healthy children (n, 120; aged 3-13 yr) were assigned randomly to six groups according to the glucose concentration of the intravenous solution (0%, 2%, or 5%, at a rate of 6 ml kg(-1) x h(-1)) and the preoperative medications (4 microg/kg clonidine or placebo given 100 min before anesthesia) they were to receive. The plasma concentrations of glucose, nonesterified fatty acid, ketone bodies, epinephrine, norepinephrine, and cortisol were determined. RESULTS: Infusion of 5% glucose caused hyperglycemia (mean glucose concentration >200 mg/dl) in six children receiving placebo and two receiving clonidine. Although the mean plasma glucose concentration increased in three placebo groups, it was unchanged and the plasma concentrations of total ketone bodies and nonesterified fatty acid were increased in children receiving clonidine and glucose-free solution. The plasma epinephrine, norepinephrine, and cortisol levels in children receiving placebo increased in response to surgery. Clonidine attenuated the increase in catecholamines and cortisol. CONCLUSIONS: Oral clonidine premedication attenuated the hyperglycemic response, probably by inhibiting the surgical stress-induced release of catecholamines and cortisol. Infusion of 2% of glucose maintained plasma glucose concentrations within physiologic ranges in children receiving clonidine.     

Benzodiazepine withdrawal reaction in two children following discontinuation of sedation with midazolam

OBJECTIVE: To report the occurrence of recurrent benzodiazepine withdrawal reactions in two very young children following discontinuation of sedation with midazolam. CASE SUMMARY: A 15-month-old boy with apneic episodes was sedated with midazolam for 12 days with constant infusion. Half a day after discontinuation of the midazolam the boy became restless, tachycardic, and hyperpyrexic. When midazolam was readministered, all symptoms disappeared. Four days later midazolam was again discontinued and within 12 hours the same signs and symptoms reappeared. Midazolam infusion was restarted, and the signs and symptoms disappeared for the second time. After thoracotomy, a 14-day-old boy received intravenous midazolam for sedation for 29 days. Within 12 hours after discontinuation of midazolam he became restless, developed a bulging stomach secondary to aerophagia, and was vomiting. Midazolam therapy was reinstituted and continued for another 2 months by constant infusion. Thereafter, the boy was successfully weaned from artificial ventilation in 5 days under sedation with midazolam. About 12 hours after discontinuation of midazolam the boy became restless, tachycardic, again developed a bulging stomach because of aerophagia, and vomited. When the child was sedated with clorazepate by continuous infusion, the signs and symptoms disappeared. DISCUSSION: Case reports describing benzodiazepine withdrawal reaction upon discontinuation of midazolam were reviewed and compared. The symptoms observed in the children we present resemble those mentioned in the three children and two adults reported previously. Unique in the very young children in this article is the occurrence of gastrointestinal symptoms, which most likely are the result of air being swallowed secondary to severe agitation. CONCLUSIONS: Midazolam withdrawal reactions in adults and children, particularly in an intensive care unit, can be significant. Considerable caution must be taken with relatively long-term administration and abrupt discontinuation of midazolam.     

Rebound pulmonary hypertension after inhalation of nitric oxide

BACKGROUND: We describe the hemodynamic response to initiation and withdrawal of inhaled nitric oxide (NO) in infants with pulmonary hypertension after surgical repair of total anomalous pulmonary venous connection. METHODS: Between January 1, 1992, and January 1, 1995, 20 patients underwent repair of total anomalous pulmonary venous connection. Nine patients had postoperative pulmonary hypertension and received a 15-minute trial of inhaled NO at 80 parts per million. Five of these patients received prolonged treatment with NO at 20 parts per million or less. RESULTS: Mean pulmonary artery pressure decreased from 35.6 +/- 2.4 to 23.7 +/- 2.0 mm Hg (mean +/- standard error of the mean) (p = 0.008), and pulmonary vascular resistance decreased from 11.5 +/- 2.0 to 6.4 +/- 1.0 U.m2 (p = 0.03). After prolonged treatment with NO, pulmonary artery pressure increased transiently in all patients when NO was discontinued. CONCLUSIONS: After operative repair of total anomalous pulmonary venous connection, inhaled NO selectively vasodilated all patients with pulmonary hypertension. Withdrawal of NO after prolonged inhalation was associated with transient rebound pulmonary hypertension that dissipated within 60 minutes. Appreciation of rebound pulmonary hypertension may have important implications for patients with pulmonary hypertensive disorders when interruption of NO inhalation is necessary or when withdrawal of NO is planned.     

Potentiation of sufentanil by clonidine in PCEA with or without basal infusion

The purpose of the present study was to observe whether inflammatory mediators, such as: Prostaglandin E2 (PGE2), Bradykinin (BK), Histamine (HIS), Platelet active factor (PAF) and 5-hydroxytryptamine (5-HT), directly triggered the release of CGRP from perivascular nerves in isolated rat mesenteric arterial bed. The results showed that PGE2 (1-100 mumol/L) and BK (5-10 mumol/L) caused time- and concentration-dependent CGRP release, but HIS, PAF and 5-HT did not show significant effects. Our data indicate that PGE2 and BK are the major inflammatory mediators in triggering the release of CGRP from the perivascular CGRP-containing nerve.     

Plasma levels of clonidine following epidural bolus injection in children

PURPOSE: To describe dense vitritis as the primary manifestation of ocular syphilis in three human immunodeficiency virus (HIV)-positive patients and to determine the response of these patients to the established regimen for neurosyphilis. METHODS: Anti-Toxoplasma gondii IgM and IgG antibody titers, tuberculin skin test, chest radiograph, and serum angiotensin-converting enzyme level were obtained because tuberculosis, sarcoidosis, and toxoplasmosis were in the differential diagnosis. Two of the three patients were not known to have HIV infection at the time of initial examination and consented to HIV testing. Treponemal and nontreponemal tests were performed on serum and cerebrospinal fluid to establish a definitive diagnosis. Treatment for neurosyphilis was initiated, and daily ophthalmic examinations were performed, with careful attention to signs commonly associated with syphilitic eye disease. RESULTS: All three patients exhibited improvement in visual acuity and resolution of vitreous haze. There was no evidence of other signs of posterior uveitis. The one patient for whom there has been a 6-month follow-up showed no sequelae of his eye disease. CONCLUSIONS: Human immunodeficiency virus-positive patients with syphilis may present atypically dense vitritis. In these patients, vitritis may be the first manifestation of syphilis. The regimen for neurosyphilis provides effective therapy. Moreover, in some patients, syphilitic vitritis may be the initial manifestation of HIV disease.     

Context-specific morphine withdrawal in rats: Duration and effects of clonidine.

Rats previously injected with morphine in a particular environment (paired rats) emitted more withdrawal symptoms in that environment than did rats previously injected with morphine in another environment (unpaired rats) after both 1 day and 5 days of morphine abstinence. Thus, reexposure to an environment previously associated with morphine can elicit context-specific withdrawal even after several days of morphine abstinence. Clonidine (0.06 mg/kg) reduced most of the withdrawal symptoms seen 5 days after morphine abstinence in both the paired and unpaired rats. However, clonidine enhanced many of the withdrawal symptoms in both groups of rats during naltrexone-precipitated withdrawal 1 day after morphine abstinence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Caudal clonidine and bupivacaine for combined epidural and general anaesthesia in children

BACKGROUND: Clonidine produces analgesia by actions on alpha 2-adrenoceptors and enhances both sensory and motor blockade from epidural injection of local anaesthetics. Low-dose clonidine has been used so far for caudal injection in children. Our aim was to study the perioperative effects of high-dose caudal clonidine when added to low concentration of bupivacaine for combined epidural and general anaesthesia in children. METHODS: After induction of general anaesthesia caudal block was performed either with 1 ml.kg-1 bupivacaine 0.175% with the addition of clonidine 5 micrograms.kg-1 (n = 20), or with 1 ml.kg-1 bupivacaine 0.175% (n = 20). The intraoperative anaesthetic requirements, the perioperative haemodynamic effects, respiratory rate, sedation score, postoperative pain scores and side effects were assessed by a blinded observer. A patient-controlled analgesia system was used for postoperative pain relief. The quality of postoperative pain relief was assessed using Smiley's pain analogue scale. RESULTS: Intraoperative haemodynamic responses did not differ between the groups. However, during emergence from general anaesthesia children in the clonidine group had significantly lower heart rates and blood pressure compared to children in the control group. In addition, heart rates and blood pressures were also lower in the clonidine group in the early postoperative period (P < 0.05). Postoperative analgesia was significantly better in the clonidine group as evidenced by the total number of requests (3 vs 12, P < 0.05) and the total amount of tramadol (20.5 mg vs 72.8 mg, P < 0.05) administered. The duration of the caudal analgesia was significantly longer in the clonidine group (20.9 +/- 7.4 h vs 14.4 +/- 10.9 h, P < 0.05). CONCLUSION: Our results suggest that caudal clonidine 5 micrograms.kg-1 enhances and prolongs caudal blockade with bupivacaine (1.175% in children. It also blocks sympathoadrenergic responses during emergence from anaesthesia. Sedation and cardiovascular effects are observed up to 3 h into the postoperative period.     

Midazolam improves postoperative epidural analgesia with continuous infusion of local anaesthetics

BACKGROUND: A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined. AIM: To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer. METHODS: Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and 14C-urea breath test) were randomized into three treatments groups: (1) LAS (n=21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n=18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n=21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication. RESULTS: Intention-to-treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks. CONCLUSIONS: High H. pylori eradication rates were achieved using the amoxycillin- and clarithromycin-based therapies. Fewer side-effects, better compliance and low cost favoured the amoxycillin-based therapy.     

Dose-response relationship of clonidine with epidural administration of ropivacaine in orthopedic procedures of the lower extremities

OBJECTIVE: The aim of this study was to investigate preliminarydose-range effects of clonidine added to ropivacaine for epidural analgesia in elective orthopedic surgery of the lower limbs with doses, causing a minimum of cardiovascular side effects. METHODS: 60 patients were randomly assigned to receive in a double-blind fashion a mixture of 1 mg/cm height ropivacaine plus saline or 1 mg/cm ropivacaine plus 25 micrograms, 50 micrograms, 75 micrograms, 100 micrograms or 150 micrograms clonidine for epidural analgesia. The sensory and motor function were determined at defined time intervals for 30 minutes. Heart rate and blood pressure were controlled and sedation score was judged. The postoperative 2-segment-regression of pin-prick and the onset of pain were recorded. RESULTS: The six groups were comparable in demographic data and in term of onset time. The prolongation of analgesia reached 513 +/- 92 min (p = 0.002) for 150 micrograms clonidine, 460 +/- 148 min (p = 0.073) for 100 micrograms clonidine, 440 +/- 86 min (p = 0.057) for 75 micrograms clonidine compared with 347 +/- 114 min for saline. In an equal manner, 2-segment-regression for pin-prick was extended to 251 +/- 47 min (p = 0.018) for 150 micrograms clonidine, 238 +/- 33 min (p = 0.034) for 100 micrograms clonidine, 229 +/- 29 min (p = 0.027) for 75 micrograms clonidine and 178 +/- 43 min for saline. Heart rate dropped down in all groups. Mean arterial pressure decreased significantly in the groups with 75, 100 and 150 micrograms clonidine. Sedation score increased continuously from 0.6 +/- 0.5 (saline) to 1.8 +/- 0.8 (150 micrograms clonidine). CONCLUSION: We conclude that 150 micrograms clonidine significantly enhances the duration of analgesia of epidurally administered ropivacaine in a mean of 171 mg. This time interval is longer than the one with 200 mg ropivacaine alone. But, there are side effects in form of decrease of arterial pressure. Cardiovascular monitoring seems to be essential. Because of the enhanced analgesia duration, the time interval for reloading epidural anaesthesia are increased.     

Acute psychosis associated with abrupt withdrawal of carbamazepine following intoxication

Carbamazepine is regularly used in the treatment of trigeminal neuralgia. Although exacerbation of psychosis has been described following abrupt discontinuation of carbamazepine in chronic schizophrenics, a withdrawal syndrome has not been reported previously in patients treated for trigeminal neuralgia. The case presented here suggests that abrupt withdrawal of toxic concentrations of carbamazepine may precipitate a withdrawal reaction, which is manifest some days after discontinuation of the drug. Therefore it may be advisable to withdraw therapy slowly in these situations.     

Neuroleptic malignant syndrome associated with abrupt withdrawal of anticholinergic agents

Oral manifestations are present in about 3-5% of cases of non-Hodgkin's lymphoma (NHL) and oral lesions are only rarely the initial manifestations of NHL. A case is presented of an 80-year-old patient with a NHL of the tongue, without visceral or lymph node involvement. The diagnosis of NHL can be made only by biopsy. The prognosis of NHL seems to be related to the tumour stage, tumour aggressiveness and response to treatment: the oral lesions appear to respond quite well to irradiation.     

The optimal test dose of epinephrine for epidural injection with lidocaine solution in awake patients premedicated with oral clonidine

We attempted to determine the optimal test dose of epinephrine for use with epidural anesthesia in awake patients premedicated with clonidine. Eighty-eight adult patients were randomized into two groups [oral premedication with clonidine 5 microg/kg (CLON) or no premedication (CONT)]. Before induction of general anesthesia, heart rate (HR) and blood pressure (BP) were measured for 3 min after the i.v. injection of 3 mL of 1.5% lidocaine containing epinephrine (0, 1.25, 2.5, 5, 7.5, or 15 microg) in a randomized, double-blind manner. We calculated 95% confidence intervals for the peak HR and BP increases induced by each dose of epinephrine. At 7.5 microg, epinephrine induced a significantly greater increase in HR and BP in CLON than in CONT. The 95% confidence interval for the HR change induced by 7.5 microg of epinephrine in CLON was nearly the same as the accepted standard dose of epinephrine (15 microg) in CONT. We conclude that premedication with clonidine enhances HR and BP responses to the i.v. administration of epinephrine-containing epidural test solutions. Consequently, 7.5 microg of epinephrine may be sufficient to enable detection of accidental injection into a blood vessel in awake patients premedicated with clonidine 5 microg/kg. Implications: Clonidine, a commonly used preanesthetic medication, alters patients' cardiovascular responses to drugs such as epinephrine. Our randomized, double-blind study suggests that, in awake patients receiving oral clonidine premedication, 7.5 microg of epinephrine (half the usual dose) is adequate as an indicator of accidental injection into the epidural vessels during epidural anesthesia.