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.     

The effect of supervision of residents on quality of care in five university-affiliated emergency departments

BACKGROUND: The purpose of the study was to compare the analgesic and side effects of two epidurally administered mixtures of bupivacaine and fentanyl with the same drug ratios. METHODS: One hundred patients scheduled for colorectal surgery were randomized to receive a thoracic epidural infusion of either bupivacaine 0.12% with fentanyl 2 micrograms/ml or bupivacaine 0.24% with fentanyl 4 micrograms/ml during 48 h postoperatively. The pumps were adjusted to keep the visual analogue scale (VAS) pain score at 3 or less (on a scale of 0-10) with a minimum of adverse effects. RESULTS: There were no statistically significantly differences between the two groups in VAS pain scores. The average VAS pain score resting varied between 0.5 and 1, and coughing between 1.9 and 3.4. One case of respiratory depression with breathing frequency 7 occurred in each group, but none of the patients required naloxone. One patient in the low concentration group developed partial motor weakness in both legs 36 h postoperatively. Equal drug amounts--bupivacaine 10.8-11 mg/h and fentanyl 18-18.4 micrograms/h--were given in both groups throughout the study. CONCLUSIONS: Both groups had low pain scores with few and comparable adverse effects. It thus seems that the volume is not important when mixtures of bupivacaine and fentanyl in the studies concentrations are infused epidurally at a low thoracic level. Practical reasons favour the higher concentration mixture.     

The effect of clonidine on intra-operative requirements of fentanyl during combined epidural/general anaesthesia

The study evaluates the analgesic effects of epidural clonidine in patients undergoing abdominal hysterectomy under combined epidural/general anaesthesia. Forty ASA 1-2 patients were divided into two groups who received epidurally either clonidine 300 micrograms (group 1) or placebo (group 2). Anaesthesia was maintained with oxygen/nitrous oxide, a midazolam infusion, vecuronium, and boluses of fentanyl 100 micrograms administered as needed to maintain cardiovascular stability. The mean (SD) intraoperative fentanyl requirements were 2.05 (0.18) and 3.66 (0.3) micrograms.kg-1.h-1 for groups 1 and 2 respectively (p < 0.001). Patients in Group 1 had a lower heart rate after tracheal intubation and surgical incision (p < 0.02). In the recovery room, pain intensity was lower in group 1 (p < 0.003) and the mean (SD) time until analgesia request was increased from 48.5 (8.4) min in group 2 to 235.7 (33.2) min in group 1 (p < 0.001). Our results demonstrate that epidural clonidine produces decreased fentanyl requirements, improved cardiovascular stability, reduced pain intensity and effective postoperative analgesia in the recovery room.     

Clonidine and ketanserin both are effective treatment for postanesthetic shivering

BACKGROUND: Although meperidine is an effective treatment of postanesthetic shivering, its mechanism of action remains unknown. Investigation of other drugs might help clarify the mechanisms by which shivering can be controlled. Accordingly, we investigated the efficacy of clonidine, an alpha 2-adrenergic agonist, and ketanserin, a 5-hydroxytryptamine antagonist, in treating postanesthetic shivering. METHODS: First, 54 patients shivering after general anesthesia were allocated randomly to receive an intravenous bolus of saline, 150 micrograms clonidine, or 10 mg ketanserin. A second study explored the dose-dependence of clonidine. Forty shivering patients were given saline or clonidine, 37.5, 75, or 150 micrograms. RESULTS: The duration of shivering was significantly shorter in those given clonidine (2.1 +/- 0.9 min) than in the other two groups and shorter in the ketanserin group (4.3 +/- 0.9 min) than in the saline group (12.0 +/- 1.6 min). Clonidine and ketanserin significantly decreased systolic arterial blood pressure when compared to saline. Core rewarming was significantly slower in the clonidine group. In the second study, 37.5 micrograms clonidine was no more effective than saline. Two minutes after treatment, 150 micrograms obliterated shivering in all patients. Five minutes after treatment, all patients given 75 micrograms had stopped shivering. Systolic arterial pressure and heart rate decreased significantly in patients given 75 and 150 micrograms clonidine. CONCLUSIONS: Clonidine (150 micrograms) and ketanserin (10 mg) both are effective treatment for postanesthetic shivering. The effect of clonidine on shivering is dose-dependent: whereas 37.5 micrograms had no effect, 75 micrograms clonidine stopped shivering within 5 min.     

Expression of LECAM-1 and LFA-1 on pre-B lymphoma cells but not on preneoplastic pre-B cells in SL/KH mice

BACKGROUND AND OBJECTIVES: The efficacy of operatively administered spinal neostigmine to provide analgesia and that of different antiemetics to prevent neostigmine-related nausea and vomiting were evaluated in patients undergoing tibial or ankle reconstruction. METHODS: One hundred patients were randomized to five groups (n = 20). The intravenous antiemetic test drug (except propofol) was given as premedication in the holding room, after intravenous midazolam, 0.05 mg/kg. The subarachnoid drugs administered were 20 mg bupivacaine (0.5%) in conjunction with 100 micrograms neostigmine, except for the saline group (S group), which received bupivacaine and saline. The S group, the neostigmine group (N group), and the propofol group (P group) received saline as the intravenous test drug. The droperidol group (D group) received intravenous droperidol 0.5 mg, and the metoclopramide group (M group) received intravenous metoclopramide 10 mg. The P group had a continuous intravenous propofol infusion (2-4 mg/kg/hr), started 10 minutes after the spinal injection. Nausea, emetic episodes, and the need for analgesic (disclofenac) or antiemetic medication were recorded for the first 24 hours following surgery and scored by a 10-cm visual analog scale (VAS). RESULTS: Subarachnoid neostigmine 100 micrograms did not affect subarachnoid bupivacaine analgesia as measured by time to first rescue analgesic in most patients, but it decreased the overall 24-hour visual analog scale (VAS) scores and the need for postoperative analgesics in 24 hours (P < .001). The incidence of intraoperative nausea and vomiting was higher in the N, D, and M groups than in the S group (P < .001). Following surgery, the 3-hour VAS assessment for emesis was higher for the N, P, and M groups than for the S group (P < .05). The overall 24-hour assessment was similar among groups. CONCLUSIONS: Subarachnoid neostigmine reduced postoperative pain scores and analgesic requirements. Whether it prolonged the duration of action of diclofenac or enhanced the mechanisms involved in spinal analgesia cannot be determined from these data. Although propofol and droperidol appeared to be more effective during and after surgery, respectively, all neostigmine groups were associated with a high consumption of antiemetics.     

Postoperative analgesia after co-administration of clonidine and morphine by the intrathecal route in patients undergoing hip replacement

Postoperative analgesia after intrathecal co-administration of clonidine hydrochloride (75 micrograms) and morphine sulfate (0.5 mg) was compared with analgesia produced after either intrathecal morphine (0.5 mg) or 0.9% sodium chloride in 90 patients undergoing total hip replacement under bupivacaine spinal anesthesia. Patient-controlled morphine requirements were significantly reduced (P < 0.001) postoperation by both clonidine/morphine (median 5 mg/24 h) and morphine (median 7 mg/24 h) compared with control (saline) (median 28 mg/24 h). However, no significant additional reduction in postoperative analgesic requirements was shown with the clonidine/morphine combination compared with morphine alone. Visual analog pain scores, although good in all groups at all times, were significantly poorer in the control group at 2 h (P < 0.04) and 4 h (P < 0.001) after operation compared with both treatment groups, and significantly poorer than the clonidine/morphine group at 6 h (P < 0.002) and 24 h (P < 0.009) postoperation. Mean arterial blood pressure was significantly lower in the clonidine/morphine group than in the two other groups (P < 0.001) between 2 and 5 h after operation. The incidence of emesis was similar in the clonidine/morphine and morphine groups and was significantly more than in the control group.     

The haemodynamic effects of rocuronium and vecuronium are different under balanced anaesthesia

BACKGROUND: Rocuronium has been reported to have minimal haemodynamic effects. However, this conclusion has been drawn primarily from investigations conducted under narcotic-based anaesthesia. This study was designed to evaluate the cardiovascular effects of rocuronium under isoflurane/N2O/fentanyl anaesthesia and to compare rocuronium's haemodynamic effects to those of vecuronium and pancuronium. METHODS: Anaesthesia was induced with fentanyl 2 micrograms/kg, thiopentone 4 mg/kg, and suxamethonium 0.5 mg/kg in 75 ASA I or II patients. After tracheal intubation, anaesthesia was maintained with isoflurane 0.5% and N2O 50% in oxygen. Five min after intubation (baseline), patients randomly received either vecuronium 100 micrograms/kg, rocuronium 600 micrograms/kg, rocuronium 900 micrograms/kg, rocuronium 1200 micrograms/kg, or pancuronium 140 micrograms/kg. One min after administration of muscle relaxant, mean arterial pressure (MAP) and heart rate (HR) were recorded and were subsequently measured at 1-min intervals for the next 4 min. RESULTS: HR decreased significantly (P < 0.05) at all times compared to baseline in patients receiving vecuronium. HR significantly (P < 0.05) increased in those receiving rocuronium 1200 micrograms/kg or pancuronium. Patients who received vecuronium had a significant (P < 0.05) decrease in MAP at all times compared to baseline. Comparing results between groups, patients who received rocuronium or pancuronium had significantly (P < 0.05) higher MAP compared to those administered vecuronium. CONCLUSION: The haemodynamic effects of rocuronium and vecuronium are different under balanced anaesthesia. Rocuronium may attenuate the fall in MAP that often occurs under balanced anaesthesia without surgical stimulation.     

Comparative study of epidurally administered clonidine and buprenorphine on anesthetic requirement and electroencephalographic activity

The author investigated the effects of epidurally administered buprenorphine (BPN) and clonidine (CLO) on the potentiation of halothane anesthesia in terms of the minimum alveolar concentration (MAC), hemodynamics, and electroencephalographic activity in the patients undergoing lower abdominal surgery. Thirty-four women (ASA-1) were studied after the epidural administration of either 10 ml saline (group A, n = 8), 10 ml saline with 0.4 mg BPN (group B, n = 13), or 10 ml saline with 150 micrograms CLO (group C, n = 13). The MAC of halothane was reduced by 32% in group B (p < 0.05), and by 23% in group C (p < 0.05) compared with group A. The delta activity on the electroencephalogram (EEG) was more dominant in groups B and C 20 and 30 minutes after the administration of BPN and CLO compared with group A. The alpha activity in group A was significantly greater than that in the other groups. The delta activity in groups B and C was increased significantly compared with group A. The blood pressure was significantly lower after the epidural administered of CLO in group C, compared with groups A and B. The study concluded that epidurally administered CLO significantly reduce the MAC of halothane and also resulted in significant acceleration of delta activity on the EEG, as did BPN. The mechanisms by which the central nervous system (CNS) is depressed by epidural BPN and CLO are different, but this may have resulted from their direct action on the CNS via the systemic and spinal absorption of BPN and CLO.     

ST segment changes in the ECG. Anesthesia induction with propofol, etomidate or midazolam in patients with coronary heart disease

Induction of anaesthesia with propofol and fentanyl can lead to marked reductions in mean arterial pressure (MAP) and heart rate (HR). Thus, the application of propofol in patients with severely reduced coronary artery perfusion is controversial. METHODS. The study group consisted of 60 patients undergoing coronary artery bypass grafting (CABG). Anaesthesia was induced over 30 s with propofol (P 1.5 mg/kg), etomidate (E 0.3 mg/kg), or midazolam (M 0.15 mg/kg) following a bolus dose of fentanyl (5 micrograms/kg). Vecuronium was used as a muscle relaxant. During induction we continuously measured MAP and HR and recorded the occurrence of myocardial ischaemia using an automatic ST-segment analyser (Marquette 7010). ST-segment deviations of more than 1 mm in leads II and V5 were interpreted as significant signs of myocardial ischaemia. RESULTS. All groups showed reductions in MAP and HR on induction that were marked in the P group. Intubation caused elevation of MAP and HR to pre-induction levels (HR: all groups) or slightly above (MAP: E, M). Four patients in the P group and 3 in each other group showed significant ST-segment deviation prior to induction. In the P group these deviations disappeared in 2 patients after injection while they remained unchanged in the M group. In the E group injection had no effect on the ischaemic ECG changes but produced another case of significant ST-segment deviation. Laryngoscopy and intubation produced no further significant ST-segment deviation in either group. DISCUSSION. Induction is a critical phase of anaesthesia, especially in patients with limited coronary reserve. Induction agents should alleviate the stress response while causing minimal haemodynamic changes. Despite marked reductions in MAP in the P group, the number of patients with ischaemic ECG changes was cut by half. Their number was unchanged or even raised in the other groups. After application of P, with an alleged reduction of coronary perfusion, a compensational reduction in myocardial oxygen consumption may occur.     

Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities

BACKGROUND: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. METHODS: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. RESULTS: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. CONCLUSIONS: Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.     

Prophylactic nefopam administration for post-anesthetic shivering

PURPOSE: Shivering is a frequent postanaesthetic complication. Its definite reason is unknown. Patients with cardiovascular or pulmonary diseases are endangered by postanaesthetic shivering. The aim of this study was to assess the efficacy of nefopam in prophylaxis of shivering. Additionally we investigated the influence of nefopam on haemodynamic parameters and on the time until extubation. METHODS: 30 patients (ASA I-II) were randomly allocated in a double-blind fashion to one of two groups to receive directly after the end of isoflurane application either nefopam (0.15 mg/kg) or placebo (0.9% saline). The period of anaesthesia had to be longer than 60 minutes. All patients received a premedication with lorazepam (0.02 mg/kg) 30-45 minutes prior to surgery. Induction of anaesthesia was standardised: fentanyl (3 micrograms/kg), thiopentone (5 mg/kg), atracurium (0.4 mg/kg). Intraoperatively a mixture of isoflurane, nitrous oxide (60%) and oxygen was used to maintain anaesthesia. The following parameters were evaluated: Age, sex, duration of operation and anaesthesia and the time between the end of application of volatiles and extubation. Heart rate (HR), mean arterial blood pressure (MAP), rectal temperature and O2-saturation were measured at predefined data points. Postoperatively the consumption of analgesic was documented. The severity of shivering was classified in five grades. RESULTS: In the control-group nine patients shivered (60%), whereas in the nefopam group only one patient (6.6%) shivered (p < 0.05). In comparison to the placebo group we observed in the nefopam group a significantly decreased HR 30 and 60 minutes postoperatively (p < or = 0.007 and p < or = 0.002). We did not observe prolonged awakening in the nefopam-treated patients. MAP and O2-saturation showed similar reactions in both groups. CONCLUSION: The data indicate that prophylactic administration of nefopam can suppress postanaesthetic shivering. Prolonged awakening was not observed.     

Effectiveness of polyclonal and monoclonal antibodies prepared for an immunoassay of the etofenprox insecticide

The aim of this study was to compare hemodynamic responses to intubation and pin head-holder application in two groups of neurosurgical patients given oral clonidine (3 microg/kg) or oral temazepam (10-20 mg) 90 min before the induction of anesthesia. Fifty patients undergoing elective craniotomy were randomized to either group. Anesthesia was induced with i.v. propofol 1500 mg/h, fentanyl 4 microg/kg, vecuronium 0.15 mg/kg, and lidocaine 1.5 mg/kg and was maintained with propofol 6 mg x kg(-1) x h(-1). Mean arterial blood pressure (MAP) and heart rate were recorded before the induction of anesthesia and before and after intubation and application of the pin head holder. Interventions required to maintain hemodynamic stability were compared between groups. Preinduction sedation scores and MAP values were similar between groups. MAP was significantly lower (P = 0.031) in the clonidine group after pin head-holder application. Interventions to stabilize MAP were not significantly different between groups (P = 0.11). We conclude that clonidine is effective in reducing the MAP increase with pin head-holder application in patients undergoing craniotomy. Implications: In this study, we investigated an approach to the prevention of increased blood pressure often seen during the early part of anesthesia for brain surgery. Oral clonidine was effective in reducing the mean arterial blood pressure increase resulting from pin head-holder application. Clonidine, a blood pressure-reducing drug, was given to 25 patients before anesthesia. Their blood pressure measurements were then compared with those of 25 patients not given clonidine.     

Postoperative analgesia in herniated disk surgery. Comparative study of diclofenac , lysine acetylsalicylate, and ketorolac

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in treating musculoskeletal pain and are theoretically ideal for treating postoperative pain of the lumbar column. OBJECTIVES: To compare the analgesic efficacy and side effects of treatment with 3 NSAIDs (lysine acetylsalicylate, ketorolac and diclofenac) in the treatment of pain after surgery for lumbar disc hernia. PATIENTS AND METHODS: We enrolled 75 ASA I-II patients undergoing discectomy because of lumbar disc hernia; balanced general anesthesia was used in all cases. The patients were randomly distributed in 3 groups based on type of analgesia given in the immediate postoperative period. Group A received lysine acetylsalicylate (1800 mg), group B received ketorolac (30 mg) and group C received diclofenac (75 mg). The analgesics were diluted in 100 mg of saline solution and administered through a peripheral vein over 10 min. We evaluated the analgesia attained on a visual analog scale (VAS) and the physiological response to pain was assessed by monitoring changes in arterial pressure, heart rate and breathing frequency. If analgesia was insufficient 30 min after administration of the drug, 200 mg of lysine cloximate was given as a top-up. The side effects of each drug were also recorded. RESULTS: VAS evaluation showed significant reductions in pain 60 min after administration in groups A and B and after 120 min in group C. Nine patients in each group required lysine cloximate. There were no significant differences in physiological response among the 3 groups. No patient suffered major side effects. Mild side effects were reported most often in group B. CONCLUSIONS: The NSAIDs studied were inadequately for treating pain after surgery for lumbar disc hernia. Ketorolac was no better than the other analgesics studied but was associated with a higher number of mild side effects.     

Effects of sufentanil on cerebral hemodynamics and intracranial pressure in patients with brain injury

BACKGROUND: The current study investigates the effects of sufentanil on cerebral blood flow velocity and intracranial pressure (ICP) in 30 patients with intracranial hypertension after severe brain trauma (Glasgow coma scale < 6). METHODS: Mechanical ventilation (FIO2 0.25-0.4) was adjusted to maintain arterial carbon dioxide tensions of 28-30 mmHg. Continuous infusion of midazolam (200 micrograms/kg/h intravenous) and fentanyl (2 micrograms/kg/h intravenous) was used for sedation. Mean arterial blood pressure (MAP, mmHg) was adjusted using norepinephrine infusion (1-5 micrograms/min). Mean blood flow velocity (Vmean, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system. ICP (mmHg) was measured using an epidural probe. After baseline measurements, a bolus of 3 micrograms/kg sufentanil was injected, and all parameters were continuously recorded for 30 min. The patients were assigned retrospectively to the following groups according to their blood pressure responses to sufentanil: group 1, MAP decrease of less than 10 mmHg, and group 2, MAP decrease of more than 10 mmHg. RESULTS: Heart rate, arterial blood gases, and esophageal temperature did not change over time in all patients. In 18 patients, MAP did not decrease after sufentanil (group 1). In 12 patients, sufentanil decreased MAP > 10 mmHg from baseline despite norepinephrine infusion (group 2). ICP was constant in patients with maintained MAP (group 1) but was significantly increased in patients with decreased MAP. Vmean did not change with sufentanil injection regardless of changes in MAP. CONCLUSIONS: The current data show that sufentanil (3 micrograms/kg intravenous) has no significant effect on middle cerebral artery blood flow velocity and ICP in patients with brain injury, intracranial hypertension, and controlled MAP. However, transient increases in ICP without changes in middle cerebral artery blood flow velocity may occur concomitant with decreases in MAP. This suggests that increases in ICP seen with sufentanil may be due to autoregulatory decreases in cerebral vascular resistance secondary to systemic hypotension.     

Oral clonidine premedication reduces vomiting in children after strabismus surgery

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3-12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg.kg-1, clonidine 2 micrograms.kg-1, and clonidine 4 micrograms.kg-1. These agents were administered 93-112 min (mean; 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen. Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 micrograms.kg-1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1.37% and 3, and 34% and 2 in clonidine 4 micrograms.kg-1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 micrograms.kg-1 vs placebo and diazepam). However, low-dose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 micrograms.kg-1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.     

Association between hemodynamic parameters and the degeneration of sustained ventricular tachycardias into ventricular fibrillation in rats

Sustained ventricular tachycardias (VT) often degenerate into ventricular fibrillation (VF). In the present study, the impact of VT on mean arterial blood pressure (MAP), myocardial blood flow (MBF), and myocardial oxygen consumption (MVCO2) was assessed. In addition, the degeneration of sustained VT into VF was analysed with respect to MAP. MBF was measured in 48 anesthetized rats with colored microspheres; arterial catecholamine levels were measured by HPLC in 16 additional rats during control conditions and VT. MBF (4. 66+/-1.29 ml/g/min; mean+/-s.d.) did not change with the onset of VT (5.37+/-1.92 ml/g/min, n.s.). Epinephrine (0.22+/-0.13 ng/ml) and norepinephrine (0.37+/-0.12 ng/ml) increased during VT (3.55+/-2.68 ng/ml, P<0.01; 0.88+/-0.44 ng/ml, P<0.05), respectively. VF was more frequent when MAP remained normal (MAP>80 mmHg: 26%) than with hypotension (MAP<80 mmHg: 2%, P<0.05). Mechanical failure was observed in 10% of rats with severe hypotension (MAP<60 mmHg), and 2% with moderate hypotension (MAP 60-80 mmHg). The endo-epicardial MBF ratio in the VF group was significantly lower than that in the non-VF group (0.94+/-0.17 v 1.11+/-0.24, P<0.05). Conclusions: severe hypotension predisposes to the occurrence of acute mechanical failure during VT; moderate hypotension during VT, however, serves as a protective mechanism against VF in structurally normal hearts. Subendocardial hypoperfusion in the presence of an increased energy demand during VT is suggested to be responsible for the initiation of VF.     

Visualization of serum albumin on electrophoretic gels using the specific ligand bilirubin

Although oral clonidine premedication is known to reduce the hemodynamic response under general anesthesia, effects of the hemodynamic response during sedated fiberoptic nasal intubation have not yet been examined. Our aim was to compare the effects of clonidine premedication on hemodynamic responses with those of atropine and hydroxyzine premedication during sedated fiberoptic nasal intubation. Thirty adult patients were randomly assigned to one of two groups: Group 1 patients (n = 15) were premedicated with atropine sulfate (0.01 mg/kg) and hydroxyzine hydrochloride (1mg/kg) intramuscularly, and group 2 patients (n = 15) were premedicated with clonidine (5 micrograms/kg) orally. We compared the hemodynamic response and sedation level in fiberoptic nasal intubation between the two groups. there were no significant differences in sedation levels and postoperative complaints between the two groups. But the oral clonidine premedication (Group 2) blunted hemodynamic changes during the fiberoptic intubation. No profound hypotension or marked bradycardia was noted in group 2. We concluded that the oral clonidine premedication might contribute to hemodynamic stability during sedated fiberoptic nasal intubation.     

Enhancement of pressor response to intravenous phenylephrine following oral clonidine medication in awake and anaesthetized patients

Clonidine, an alpha 2-adrenergic agonist, augments the pressor response to intravenous ephedrine. If this effect is partly due to clonidine-induced potentiation of alpha 1-adrenoceptor-mediated vasoconstriction, it is also assumed that clonidine would enhance the pressor effect of phenylephrine as an alpha 1-adrenergic agonist. The authors studied haemodynamic responses to intravenous phenylephrine in 80 patients who received either preanaesthetic medication with clonidine approximately 5 micrograms.kg-1 po (clonidine group, n = 40), or no medication (control group, n = 40). Each group was further divided into either awake subjects (n = 20) or subjects anaesthetized with enflurane and nitrous oxide in oxygen (n = 20). Haemodynamic measurements were made at one-minute intervals for ten minutes after phenylephrine 2 micrograms.kg-1 iv was injected as a bolus. The magnitudes of maximal mean blood pressure increases in the clonidine group (26 +/- 7% (mean +/- SD) for awake and 32 +/- 15% for anaesthetized subjects) were greater (P < 0.05) than in the control group (13 +/- 7% for awake and 18 +/- 7% for anaesthetized subjects). However, there was no difference in the pressor effect of phenylephrine between awake and anaesthetized patients in both groups. Oral clonidine preanaesthetic medication, 5 micrograms.kg-1, augments the pressor responses to phenylephrine 2 micrograms.kg-1 iv in awake and anaesthetized patients. These results suggest that the enhancement of the pressor responses to phenylephrine following oral clonidine may be due to clonidine-induced potentiation of alpha 1-adrenoceptor-mediated vasoconstriction. This implies that restoration of blood pressure can be achieved effectively by phenylephrine in hypotensive patients with clonidine premedication.     

Drug-induced gingival hyperplasia and its management--a literature review

The purpose of our study was to find out whether patient-controlled epidural administration (PCEA) of a mixture containing a low-dose local anaesthetic, opioid and alpha 2-agonist provides as good or better postoperative analgesia as continuous epidural administration of the same analgetic solution. METHODS: 30 patients (ASA I-III), scheduled for major abdominal surgery, were randomly divided into 2 groups. 90 minutes after induction of general anaesthesia all patients received a continuous epidural infusion of 5 ml/h of the analgetic solution (50 micrograms sufentanil + 150 micrograms clonidine in 50 ml 0.125% bupivacaine) until the end of surgery. Immediately postoperatively the patients of group A received a continuous infusion of the study solution (5-8 ml/h), the patients of group B received a baseline continuous epidural infusion (3 ml/h), additionally they could self-administer 5 ml boli via a PCEA device. Measurements included the total dose of infused drug solution, pain at rest and on exercise by a visual analogue scale, cardiorespiratory data and side effects within the first 24 hours postoperatively. A standardised interview on analgesia and side effects was held 2 days after surgery. RESULTS: The PCEA group demanded less epidural analgesics (gr. B: 112 +/- 33 ml vs. gr. A: 135 +/- 20 ml) p < 0.01). Both continuous epidural infusion and patient-controlled administration provided very good analgesia at rest (gr. A: VAS 0.4 +/- 0.4 and gr. B: VAS 0.4 +/- 0.5) (n.s.). On exercise continuous epidural infusion of analgesics resulted in significantly lower pain scores (gr. A: 1.9 +/- 1.1) than patient-controlled application (gr. B: 3.4 +/- 1.1) (p < 0.01). We did not notice severe side effects such as respiratory depression or drop of heart rate or blood pressure. CONCLUSION: In patients at rest both continuous and patient-controlled epidural administration of analgesics provides excellent analgesia after major abdominal surgery. Contrariwise, patients on exercise who could use a PCA-device experienced more pain compared to those with a continuous epidural infusion technique. On the other hand the patients of the PCA-group consumed less epidural analgesics. We did not notice any severe side effects such as respiratory depression or cardiovascular instability during the study.     

Level concept of analgesic dosing in intensive care medicine with sufentanil

OBJECTIVE: The efficacy of a 3-level regimen of analgesia and sedation was investigated in a clinical setting. Level 1 consisted of continuous administration of sufentanil, in level 2 continuous administration of midazolam and level 3 continuous administration of midazolam and clonidine was added according to patients' needs. METHODS: Sufentanil at 1 microgram/kg/h was given initially. Later it was adjusted to patients' requirements in accordance with the Ramsay score (group 1). Long-term intubated patients received in addition midazolam 0.05 mg/kg/h (group 2). If needed, clonidine 1 microgram/kg/h was added (group 3). Mean drug requirements were investigated during controlled ventilation and during assisted ventilation with spontaneous breathing > 25% of total minute ventilation. In group 1 arterial paCO2 was measured to estimate drug-induced respiratory depression. Values given are median and ranges. RESULTS: With the 3-level-regimen of analgesia and sedation a Ramsay score of 2-3 was achieved in all intensive-care patients. In group 1 (n = 109; 36.7%) paCO2 values were similar at all times. Patients on controlled ventilation needed sufentanil 0.6 (0.075-2.5) microgram/kg/h, on assisted ventilation 0.4 (0.05-2.5) microgram/kg/h. Patients of group 2 (n = 113; 38.1%) had on controlled ventilation a higher requirement of sufentanil 1.2 (0.09-2.7) micrograms/kg/h, in addition Midazolam 0.05 (0.002-0.56) mg/kg/h was given. On assisted ventilation with spontaneous breathing > 25% sufentanil 0.9 (0.05-2.6) microgram/kg/h plus midazolam 0.04 (0.002-0.38) mg/kg/h was sufficient. Group 3 (n = 75; 25.2%) had on controlled ventilation a higher requirement of sufentanil with 1.5 (0.09-4.0) micrograms/kg/h and midazolam 0.05 (0.005-0.52) mg/kg/h, in addition clonidine 1.1 (0.12-2.88) micrograms/kg/h was given. On assisted ventilation with spontaneous breathing > 25% requirement of sufentanil with 1.1 (0.15-2.6) micrograms/kg/h and of midazolam with 0.05 (0.002-0.22) mg/kg/h was slightly lower, whereas more clonidine was needed with 1.3 (0.12-2.88) micrograms/kg/h. CONCLUSION: Continuous infusion of sufentanil only for analgesia and sedation is suitable for intensive-care patients with a short stay in the ICU. Respiratory depression during spontaneous breathing is not significant. The supplementary administration of midazolam and clonidine according to the presented regimen was shown to be of advantage for patients with a longer stay in ICU.