The effective duration of analgesia after intrathecal morphine in patients without additional opioid analgesia: a randomized double-blind multicentre study on orthopaedic patients.

BACKGROUND AND OBJECTIVE: To know whether the application of patient-controlled analgesia devices could be avoided if intrathecal morphine is given in combination with spinal anaesthesia. METHODS: In a randomized, double-blind multicentre study, 188 orthopaedic patients were randomized to receive intrathecally placebo, 0.1 mg morphine or 0.2 mg morphine in addition to 15 mg bupivacaine. The primary outcome parameter was the number of patients without any additional request for opioid during a period of 72 h after surgery. RESULTS: Patients with 0.1 or 0.2 mg morphine showed a significant reduction in opioid requests compared with placebo during 72 h after surgery (P = 0.0001). At 24 h after surgery, the rate of patients who required additional opioid analgesia was 71% in the placebo group, 51% in the 0.1 mg morphine group and 31% of the patients in the 0.2 mg morphine group. After 0.2 mg morphine, systemic opioid requirements at 24 h were significantly lower than those in patients with 0.1 mg morphine (P < 0.05). Intrathecal morphine was not associated with an increased frequency of respiratory depression. Forty per cent of patients with intrathecal morphine did not ask for systemic opioids. CONCLUSION: Intrathecal morphine in a dose of 0.1 and 0.2 mg provides effective analgesia for up to 48 h without any need for systemic opioids at all in many patients.

[Delayed negative pressure pulmonary edema]. / Verzögert auftretendes, postobstruktives Lungenödem.

A young athletic male adult (smoker) developed a pulmonary edema 30 min after the end of anaesthesia. Extubation was complicated by a laryngospasm. After artificial ventilation for 12 h the patient recovered completely.A negative pressure pulmonary edema (NPPE) develops after deep inspiratory efforts with an occluded airway. Such a maneuver leads to negative intrapleural pressures of -50 to -100 mmHg. This pressure gradient causes damage to the pulmonary capillaries, a transcapillary volume shift into the interstitium,and hemodynamic changes that increase the intrapulmonary blood volume. As a NPPE may occur with a delay of up to 1 h it is crucial to provide adequate monitoring for patients at risk. Symptomatic therapy usually leads to complete recovery within several hours.

Clonidine prevents sevoflurane-induced agitation in children.

UNLABELLED: In a double-blinded trial, 40 male children (age 2-7 yr) undergoing circumcision were randomly assigned to receive clonidine 2 microg/kg IV or placebo after anesthetic induction. For induction and maintenance of anesthesia, we used sevoflurane as the sole anesthetic. For pain treatment, a penile block was performed before surgery. After surgery the incidence and severity of agitation was measured during an observation period of 2 h. Severe agitation was treated with midazolam. In 16 placebo and 2 clonidine-treated patients agitation was observed (P < 0.001). In 6 patients of the Placebo group, agitation was graded as severe, whereas none of the patients in the Clonidine group developed severe agitation (P = 0.02). During the postoperative period heart rate and blood pressure were significantly decreased in clonidine treated patients (P < 0.05). We conclude that clonidine effectively prevents agitation after sevoflurane anesthesia. IMPLICATIONS: The recovery from sevoflurane anesthesia may be complicated by the presence of agitation in pediatric patients. Clonidine 2 microg/kg IV after anesthetic induction effectively reduces the incidence of agitation without resulting in clinically relevant bradycardia and hypotension.

[Prevention of "post-sevoflurane delirium" with midazolam]. / Prophylaxe des "Postsevoflurandelirs" mit Midazolam.

In a randomized double-blind placebo-controlled trial in children 2-7 years of age, we investigated the effect of a single prophylactic midazolam bolus (0.1 mg/kg b.w.) prior to the termination of anaesthesia, on the incidence and severity of agitation occurring after sevoflurane administration. Compared to the placebo group, midazolam prophylaxis significantly decreased the incidence of postanaesthetic delirium. However, the incidence of severe agitation requiring treatment was not different between the groups (placebo: n = 6; midazolam: n = 4). The mean severity of agitation was significantly lower in patients with midazolam prophylaxis. When midazolam was administered for the treatment of severe agitation it reduced the severity but did not abolish agitation. All patients were discharged from the recovery room after the 2 h observation period. From our study we conclude that a small prophylactic midazolam bolus is able to reduce the incidence and severity of agitation after sevoflurane anesthesia in some patients but is insufficiently effective in patients with severe agitation. Thus, the prophylactic administration of midazolam extenuates but does not solve the problem of post-sevoflurane agitation.

[Myocardial infarction during pregnancy]. / Myokardinfarkte in der Schwangerschaft.

Up to now 136 cases of myocardial infarction during pregnancy have been reported, and angiography revealed normal findings in 47%. In these cases coronary spasms have been discussed as the major mechanism of the disease. In isolated cases coronary artery dissection may also present with a normal coronary angiography. The case of a 31-year-old pregnant women who developed myocardial infarction during a caesarean section under spinal anaesthesia gives rise to the assumption that an early stage of coronary artery disease may be the third cause that has to be considered. Probably as a consequence of phases of tachycardia and hypertension during the course of anaesthesia, the patient developed a myocardial infarction that she survived without sequelae. While coronary angiography showed normal coronary vessels, an intravascular ultrasound study (IVUS) demonstrated an atheroma in the left main coronary artery with a ruptured fibrous cap. Laboratory screening for risk factors of coronary artery disease (CAD) showed hypercholesterinemia, increased factor VII activity and hyperfibrinogenemia. Platelet aggregation was not inhibited by acetylsalicylic acid. It was pointed out recently that even in asymptomatic patients, plaques may be present in coronary vessels indicating an early stage of CAD that cannot be diagnosed by angiography. Plaque rupture is often triggered by hypertension and may lead to myocardial infarction, instable angina pectoris, or sudden ischemic death. As IVUS is a new diagnostic tool that allows diagnoses of even early stages of CAD we believe that myocardial infarction during pregnancy is more often caused by plaque rupture than may be expected according to the current literature.

[Are there certified indications for the use of antithrombin III in intensive care]. / Gibt es gesicherte Indikationen für den Einsatz von Antithrombin III in der Intensivmedizin?

The serine-protease-inhibitor antithrombin III (AT III) has often been recommended for the therapy of septic patients as it provides anticoagulant and antiinflammatory actions. In animal studies the prophylactic treatment with AT III in a dose > 250 U/kg prevented the development of disseminated intravascular coagulopathy and vital organ dysfunction during sepsis and lowered the mortality rate. In clinical studies with septic patients therapy usually was started several hours after the start of the disease in dosages much lower than those used in animal studies. In these patients AT III-therapy improved laboratory changes of disseminated intravascular coagulopathy but was unable to lower the mortality rate. Hereditary AT III deficiency, lack of heparin effect due to low AT III levels, disseminated intravascular coagulation disorders are indications for the use of AT III while beneficial effects of AT III in patients suffering from SIRS, sepsis or septic shock have not yet been demonstrated.

Coronary artery plaque disruption as cause of acute myocardial infarction during cesarean section with spinal anesthesia.

A 31-year-old parturient delivered twins at 35 weeks' gestation by cesarean section with spinal anesthesia. Following anesthesia induction, hypotension and bradycardia occurred, and were immediately treated with theodrenaline plus cafedrin (Akrinor) and atropine. Blood pressure and heart rate increased to 180/100 mmHg and 140 beats per minute, respectively. Several minutes later, the patient developed a myocardial infarction (MI) that she survived after intensive care treatment without sequelae. Although the coronary angiography showed normal coronary vessels, an intravascular ultrasound study demonstrated an atheroma in the left main coronary artery with ruptured fibrous cap. Laboratory screening for risk factors of coronary artery disease (CAD) showed hypercholesterinemia, increased factor VII activity, and hyperfibrogenemia. Angiographically normal coronary vessels are frequently found in pregnant patients who suffered MI. In these patients, coronary spasms have been discussed as the major mechanism of disease. Our case demonstrates that a significant CAD may be present despite angiographically normal findings. Plaque rupture was triggered by hypertension and led to MI as the first symptom of disease. On the basis of these findings, we believe that MI during pregnancy is more often caused by plaque rupture than may be expected, according to the current literature.

[Inadvertent potassium chloride infusion in an epidural catheter]. / Versehentliche Infusion von Kaliumchlorid in einen Epiduralkatheter.

In a 65 years old male patient 38 cc of a 7.45% potassium chloride-solution was inadvertently infused within 3 hours into an epidural catheter on the first postoperative day. The epidural potassium chloride administration resulted in a paresis and painful paraesthesia of the patient's legs and a level of sensory blockade to TH 11. Furthermore vegetative symptoms like hypertension and tachycardia were observed. For therapy a single bolus of 40 mg dexamethasone was administered intravenously followed by an epidural infusion of sodium chloride 0.9% 99 cc/h for several hours. About 6 hours after the start of infusion all symptoms had disappeared. It is proposed that the use of colour-coded epidural catheter devices and coloured electrolyte solutions as well as infusion-pumps with a larger reservoir that reduce the frequency of syringe changes would be helpful in avoiding such complications.

[Effectiveness of autologous blood donation in coronary surgery--a retrospective analysis]. / Die Effektivität der Eigenblutspende in der Koronarchirurgie--eine retrospektive Analyse.

OBJECTIVE: This study was performed to evaluate whether autologous blood donation prior to coronary artery bypass graft surgery (cabg) reduces homologous blood requirements and the risk of homologous blood transfusion. METHODS: Within a period of 18 months, 633 patients undergoing cabg surgery were retrospectively included into the study. Non-donors were included if preoperative haemoglobin concentration exceeded 12.5 g%. RESULTS: According to demographic data, risk scores of patients who donated blood (n = 201) were lower. More patients of this group received left internal mammary bypass grafts (63% vs. 51%; p = 0.047). Nevertheless, blood loss did not differ between donors and non-donors. Prior to blood donation, haemoglobin-concentration was significantly higher in male donors (n = 177) compared to female donors (n = 24) (15 +/- 1.2 vs. 13.8 +/- 1 g%; P < 0.001). Compared to female donors, male patients donated significantly more blood units. The risk of homologous blood donation was significantly lower in male donors than in male non-donors (no homologous transfusion: 20% vs. 42%; P < 0.0001; Odds Ratio: 0.34; 95% confidence-interval: 0.23-0.52). Accordingly, homologous blood requirements were lower in male donors (0.9 +/- 3.4 vs. 1.6 +/- 3.6 blood units; P = 0.02). Between female donors and non-donors neither the number of patients treated with homologous blood (no homologous transfusion: 29% vs. 33%, P = 1; odds ratio: 1.17; 95% confidence-interval: 0.4-3.4), nor the mean number of transfused homologous blood units (1.8 +/- 1.6 vs. 1.9 +/- 2.4; P = 0.83) was different. Reactions during blood donation requiring treatment (bradycardia, hypotension, angina, arrhythmias) occurred more often in female patients (5/24 vs. 9/177; P = 0.015). CONCLUSION: In our study, autologous blood donation significantly decreased the risk of homologous transfusion and homologous blood requirements in male cabg patients. We were not able to prove the efficacy of autologous blood donation in female cabg patients. Due to the small sample size of our investigation, further prospective studies are necessary to answer the question whether patients with low blood volume, body weight and body height scheduled for cabg surgery should be excluded from autologous blood donation.

Preoperative alpha2-adrenergic receptor agonists prevent the deterioration of renal function after cardiac surgery: results of a randomized, controlled trial.

OBJECTIVE: To evaluate the influence of the alpha2-adrenergic receptor agonist clonidine on creatinine clearance as a measure of renal function. DESIGN: Prospective, double-blind, randomized, placebo-controlled clinical trial. SETTING: University hospital. PATIENTS: Patients undergoing coronary artery bypass graft surgery (n = 48) with normal risk. INTERVENTIONS: Administration of clonidine (4 micrograms/kg iv)) or placebo 1 hr before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Induction and maintenance of anesthesia (etomidate, midazolam, and fentanyl) and cardiopulmonary bypass technique (nonpulsatile, normothermic, intermittent cold blood cardioplegia) were standardized in all patients. The night before surgery and the first and third night after surgery, creatinine clearance was calculated from a 12-hr urine collection period. Venous blood samples for determination of plasma antidiuretic hormone (ADH) concentrations were taken the evening before surgery, immediately before induction of anesthesia and the evening after surgery (n = 16). Arterial catecholamine plasma concentrations were determined (high-performance liquid chromatography) before induction, 15 mins after induction of anesthesia, immediately after sternotomy, before initiation of cardiopulmonary bypass, as well as 5, 15, and 30 mins after initiation of cardiopulmonary bypass (n = 16). The total amount of anesthetics, infusions, transfusions, diuresis, and blood loss was not different between the groups. Creatinine clearance decreased over the first postoperative night from 98 +/- 18 (preoperatively) to 68 +/- 19 mL/min (p < .05) in placebo-treated patients. Creatinine clearance remained unchanged in clonidine-treated patients (90 +/- 19 [preoperatively] to 92 +/- 17 mL/min). There was a significant difference in creatinine clearance between the groups during the first postoperative night (p < .05; Mann-Whitney U test). In the third postoperative night, mean creatinine clearance of both groups was not different (75 +/- 31 vs. 86 +/- 28 mL/min). ADH concentrations were not different between the groups at any time, while plasma catecholamine concentrations were always significantly lower in clonidine-treated patients. CONCLUSIONS: Preoperative treatment with clonidine (4 microgram/kilogram) prevents the deterioration of renal function after cardiac surgery. This effect might be due to clonidine-induced reduction in the sympathetic nervous system response to coronary artery bypass graft surgery.

[Alpha 2-adrenoceptor agonists for the treatment of chronic pain]. / Alpha 2-Adrenozeptoragonisten zur Therapie chronischer Schmerzen.

The antinociceptive effect of alpha(2)-adrenoceptor agonists is mediated by activation of descending inhibiting noradrenergic systems, which modulates 'wide-dynamic-range' neurones. Furthermore, they inhibit the liberation of substance P and endorphines and activate serotoninergic neurones. Despite this variety of antinociceptive actions, there is still little experience with alpha(2)-adrenoceptor agonists as therapeutic agents for use in chronic pain syndromes. Studies in animals and patients have shown that the transdermal, epidural and intravenous administration of the alpha(2)-adrenoceptor agonist clonidine reduces pain intensity in neuropathic pain syndromes for periods varying from some hours up to 1 month. Patients suffering from lancinating or sharp pain respond best to this therapy. Topically applied clonidine (200-300 microg) relieves hyperalgesia in sympathetically maintained pain. Epidural administration of 300 microg clonidine dissolved in 5 ml NaCl 0.9 % has also been shown to be effective. In patients suffering from cancer pain tolerant to opioids, pain control has proved possible again with combinations of opioids and clonidine. In isolated cases clonidine has been administered epidurally at a dose of 1500 microg/day for almost 5 months without evidence for any histotoxic property of clonidine. Side effects often observed during administration of alpha(2)-adrenoceptor agonists are dry mouth, sedation, hypotension and bradycardia. Therapeutic interventions are usually not required.

Dose-response effects of intravenous clonidine on stress response during induction of anesthesia in coronary artery bypass graft patients.

This study was designed to evaluate the dose-response effects of different doses of clonidine on the stress response to laryngoscopy and endotracheal intubation. In a randomized, double-blind study, 48 coronary artery bypass grafting (CABG) patients received 0, 2, 4, or 6 micrograms/kg clonidine as an intravenous (IV) infusion during a 15-min period 30 min prior to induction of anesthesia with etomidate (0.3 mg/kg), fentanyl (5-7 micrograms/kg), and pancuronium (0.1 mg/kg). Sedation was assessed prior to induction of anesthesia. Cardiovascular variables and catecholamine plasma levels were measured at predefined intervals. Additional bolus doses of etomidate and fentanyl for suppression of stress-induced reactions were administered if predefined limits of heart rate and blood pressure were exceeded. Clonidine 4 and 6 micrograms/kg significantly attenuated hemodynamic and adrenergic reactions to stress, reduced pharmacologic interventions, and increased sedation. However, clonidine 6 micrograms/kg was not more effective than 4 micrograms/kg, and clonidine 2 micrograms/kg was equally effective as placebo. We conclude that clonidine 4 micrograms/kg IV is the appropriate dose to attenuate the stress response to laryngoscopy in CABG patients. Side effects limiting the use of IV clonidine were not observed.

[Does clonidine modify the hypnotic effect of propofol?]. / Beeinflusst Clonidin den hypnotischen Effekt von Propofol?

The administration of alpha 2-adrenoceptor agonists before the induction of anaesthesia leads to a significant reduction in the amount of anaesthetic medication required, probably due to an attenuation of haemodynamic stress responses in centrally mediated sympathicolysis. However, it is not yet known whether alpha 2-adrenoceptor agonists influence the hypnotic action of anaesthetics. Therefore, this study was performed to evaluate the influence of the alpha 2-adrenoceptor agonist clonidine on the potency and the duration of the hypnotic action of anaesthetic agents. METHOD. The study was approved by the local ethical committee. To study the effect of clonidine on the potency of propofol we determined the ED50 of propofol with and without clonidine pretreatment. To this end, 100 unpremedicated patients (ASA I or II) were randomly assigned to receive 4 micrograms/kg body weight clonidine or placebo, each of which was dissolved in 100 ml NaCl and infused over a period of 15 min starting 30 min before the induction of anaesthesia. According to the results of a pilot study, patients who had been treated with clonidine received either 0.25, 0.5, 0.75, 1 or 1.25 mg/kg propofol for anaesthesia induction. Patients in the placebo group received 0.5, 1, 1.5, 2 or 2.5 mg/kg propofol. The success of anaesthesia induction was evaluated clinically (eye opening on command, eyelid reflex). On the basis of these data the ED50 of propofol with and without clonidine pretreatment was calculated using the modified probit analysis according to Spearman and Kärber. The effect of clonidine on the duration of anaesthesia was compared in six groups of 10 patients each, who received 1, 1.5 or 2 mg/kg propofol for anaesthesia induction with and without prior clonidine treatment. RESULTS. In the placebo group a dose of 0.5 mg propofol per kg did not produce a hypnotic effect in any patient, while 2.5 mg propofol per kilogram of body weight was effective in all patients. In the clonidine group 0.25 mg propofol per kilogram of body weight had no hypnotic effect, while 1.25 mg propofol per kilogram of body weight was effective in all patients. Increasing the dose of propofol resulted in an increasing number of successful anaesthesia inductions in the placebo as well as in the clonidine group. According to these data, the ED50 of propofol with clonidine was calculated at 0.675 +/- 0.23 mg/kg with clonidine and 1.5 +/- 0.58 mg/kg without clonidine pretreatment. Increasing the dose of propofol did not result in a significant increase in the duration of anaesthesia (1 mg/kg: 260 +/- 114 s; 1.5 mg/kg: 270 +/- 103 s; 2 mg/kg: 295 +/- 152 s). However, premedication with clonidine almost doubled the duration of the hypnotic action of propofol (1 mg/kg: 457 +/- 239 s; 1.5 mg/kg: 501 +/- 249 s; 2 mg/kg: 582 +/- 254 s) (P < 0.01). CONCLUSION. According to these findings the administration of clonidine prior to anaesthesia induction significantly increases the potency and the duration of the hypnotic action of propofol. From our data we conclude that the influence of clonidine on the hypnotic action of anaesthetics is an important factor in the reduction of anaesthetic requirements observed after clonidine pretreatment.

Inotropic support of the critically ill patient. A review of the agents.

Intensive care patients often require inotropic support to stabilise circulation and to optimise oxygen supply. In this context, the catecholamines norepinephrine (noradrenaline), epinephrine (adrenaline), dopamine and dobutamine are still the mainstay of therapy. They provide, to different extents, a variety of adrenoceptor-mediated actions comprising vasoconstriction (via alpha-receptors) as well as vasodilatation (via beta 1-receptors), and an increase in cardiac output by enhancing inotropy and heart rate (again via beta 1-receptors). Because of their favourable pharmacokinetic profile (plasma half-lives of about 2 minutes) their actions can easily be controlled. Combinations of different catecholamines with each other or with other drugs such as phosphodiesterase inhibitors or nitrates lead to a broad spectrum of possible haemodynamic actions. However, the use of catecholamines is limited by side effects like tachycardia, hypertension and disturbances of organ perfusion caused by vasoconstriction. Furthermore, as a result of receptor downregulation during long term therapy, the efficacy of catecholamine treatment decreases. These shortfalls stimulated the search for alternatives to catecholamine treatment. Among these, phosphodiesterase inhibitors (e.g. enoximone and amrinone) appear to be the most promising drugs which have been introduced into acute clinical practice up to now. They act via inhibition of the phosphodiesterase isoenzyme III, leading to higher intracellular calcium levels by increasing cyclic adenosine monophosphate (cAMP) levels. These agents improve cardiac performance by enhancing contractility, reducing left ventricular afterload and improve diastolic relaxation. In cases of failing catecholamine therapy due to receptor downregulation, treatment with phosphodiesterase inhibitors may still be effective since their action is not receptor-mediated. Inhibition of the phosphodiesterase enzyme in vascular smooth muscle leads to vasodilatation. Therefore, in low cardiac output states combined with increased total peripheral or pulmonary vascular resistance, phosphodiesterase inhibitor therapy is particularly effective. Depending on the dosage and the speed of intravenous administration, the use of phosphodiesterase inhibitors sometimes results in pronounced decrease of blood pressure which may require vasopressor therapy. Other drugs including histamine H2-agonists are currently under investigation. Their value in the treatment of intensive care patients has still to be evaluated.

[Anesthesia induction using etomidate in a lipid emulsion]. / Narkoseeinleitung mit Etomidat in Lipidemulsion.

The use of etomidate as an anaesthetic induction agent has been hampered significantly by unwanted side effects such as pain on injection and thrombophlebitis. Investigations by Doenicke et al. have shown that the solubilizer propylene glycol is responsible for these side effects and that they can be avoided by the use of a lipid emulsion formulation. It was the goal of the present study to quantitate the reduction of thrombophlebitis and pain on injection following both formulations under double-blind study conditions. METHODS. In 100 patients anaesthesia was induced either with a new galenic formulation of etomidate--etomidate in lipid emulsion formulation (Lipofundin MCT 20%; eto-lip)--or with etomidate in propylene glycol 35% (eto-pg). Both groups received 0.3 mg kg-1 etomidate in double-blind randomized fashion. After the injection of etomidate the venous cannula was removed. The observing anaesthetist was unaware of the study drug used, to guarantee blinded investigation conditions. Discomfort and pain during and following injection were recorded, as was local skin irritation. Venous sequelae were assessed for 7 days following injection to register the occurrence of thrombophlebitis. RESULTS. Demographic data were not different between the two groups. For induction of anaesthesia the same dose of both preparations was necessary, and no difference in heart rate and blood pressure before, during or after anaesthesia induction was observed. Pain on injection (78% vs 14%), myoclonus (24% vs 8%) and local skin reaction (50% vs 6%) were present significantly more often in the eto-pg group (P < 0.01; P < 0.05 respectively, chi-square test) than in the eto-lip group. On the 1st and 2nd postoperative days, examination of the injected vein revealed a significantly higher incidence of symptoms of thrombophlebitis in the group treated with eto-pg (25% vs 3%). CONCLUSION. From these results it is concluded that in terms of vein compatibility the new galenic formulation of etomidate with lipofundin MCT 20% is superior to the propylene glycol preparation while pharmacodynamic properties seem not to be affected.

Critical care pharmacotherapy. A review.

During recent years, research in critical care medicine has focused on the role of the gastrointestinal tract in the pathogenesis of multiple organ failure and nosocomial infection, and on preventive measures. Gram-negative bacterial overgrowth of the oropharynx and stomach has been proved to be a cause of nosocomial pneumonia. Topical application of antibiotics into the oropharynx and stomach, and preservation of gastric acidity have been shown to be effective prophylaxis in ventilated patients. Recent studies have demonstrated that gastric alkalinisation is no longer necessary for the prevention of stress ulcer bleeding in critically ill patients. Tissue hypoxaemia, not gastric acidity, is the underlying pathomechanism of stress ulcer bleeding. In experimental investigations, pirenzepine and sucralfate improved gastric mucosal oxygen supply. Both compounds effectively prevent bleeding without increasing gastric pH. In mechanically ventilated patients, significantly lower rates of pneumonia occur with both of these drugs compared with antacids or histamine H2-receptor antagonists. Topical antibiotics (selective digestive decontamination) are most effective in patients with alkaline gastric juice, but of only marginal clinical relevance in those with acidic gastric contents. Isoflurane, propofol and clonidine have been recently investigated for sedation of ventilated patients. Isoflurane may lead to fluoride accumulation after more than 1 day. Propofol dosage has to be increased more often after 4 to 7 days, leading to fat overload and significantly increased costs. Clonidine was highly effective in patients with 'sympathetic overshoot', e.g. those experiencing alcohol or opioid withdrawal. Wound infections are an important problem in burn patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Lidocaine plus fentanyl for controlling cardiovascular reactions to laryngoscopy and intubation]. / Lidocain plus Fentanyl zur Dämpfung der kardiovaskulären Reaktion auf Laryngoskopie und Intubation.

Administration of fentanyl or lidocaine alone often insufficiently suppresses the haemodynamic reaction to laryngoscopy and intubation. We therefore evaluated the combination of both substances in patients with good ventricular performance (EF > 60%) undergoing coronary bypass surgery. 20 patients were randomly assigned to Group 1 (G1) or Group 2 (G2). As induction agents flunitrazepam (0.025 mg/kg), fentanyl (6-7 micrograms/kg) and pancuronium (0.1 mg/kg) were used. 3 minutes prior to intubation G1-patients received saline (0.1 cc/kg) while in G2 patients lidocaine (1 mg/kg) was administered. 10 minutes after termination of the preparations for induction (M1), prior to (M2), during (M3) and 10 minutes after the end of intubation (M4) heart rate (HR), blood pressure (MAP), pulmonary artery pressure (PAP) pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured. From these values we calculated rate-pressure product (RPP), total peripheral resistance (TPR), pulmonary vascular resistance (PVR), cardiac index (CI), stroke volume (SV) and stroke index (SI). Whitney-Mann test (U-test) served for statistical evaluation. If compared to baseline (M1), induction of anaesthesia caused in both groups a significant decrease of MAP (G1: 109 to 81 mmHg; G2: 97 to 77 mmHg), CO (G1: 6.2 to 5.2 l/min; G2: 6.6 to 5.2 l/min), CI (G1: 3.3 to 2.8 l/min m2; G2: 3.5 to 2.7 l/min m2) and RPP (G1: 12701 to 10201 mmHg min-1; G2: 11309 to 8070 mmHg min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Benzodiazepine antagonists. An update of their role in the emergency care of overdose patients.

The benzodiazepine antagonist flumazenil is a very valuable tool in the diagnosis and treatment of intoxications in which benzodiazepines are involved. In case of a positive response, patients will regain consciousness immediately, thus verifying the diagnosis and making a brief history possible to identify other drugs that might be involved. Moreover, invasive diagnostic and therapeutic procedures like gastric lavage, lumbar puncture, mechanical ventilation, etc., may then be unnecessary. In cases of pure benzodiazepine overdose a single injection of flumazenil 0.2mg should be given, followed by individually titrated increments of 0.1 mg/min until the patient is awake and responsive. In these cases a total dose of 2mg is usually sufficient. Higher doses of flumazenil may be necessary in cases of combined drug overdose. Because of its high therapeutic index, the administration of flumazenil is usually not accompanied by serious adverse effects. Benzodiazepine withdrawal syndromes characterised by transient anxiety and depression can occur, but the incidence is low. Increases of blood pressure and heart rate due to a release of catecholamines are possible, which might endanger patients with cardiovascular diseases. In severe cases, seizures have been observed which usually respond well to small doses of benzodiazepine agonists. In all cases of successful treatment it should be remembered that the effect of flumazenil deteriorates after 1 to 2h, which usually leads at first to resedation. In these patients additional bolus injections or a continuous infusion (0.1 to 0.5 mg/h) may be necessary. The effectiveness of flumazenil in cases of alcohol (ethanol) poisoning is questionable and should be further investigated.

Anaesthesia techniques for midazolam and flumazenil--an overview.

Midazolam, the latest benzodiazepine agonist, may be used in doses of 0.15 to 0.2 mg.kg-1 for induction of anaesthesia. It provides good correlation between plasma concentration and anaesthetic effect with an interindividual variability of only 20-25%. On this basis, dosage recommendations for midazolam in total intravenous anaesthesia techniques are possible, aiming at hypnotic plasma concentrations of at least 250 ng.ml-1. Due to its biological half-life of 150-180 min and interindividual differences in drug susceptibility, prolonged recovery periods have been observed that can safely and reliably be antagonised by flumazenil, if necessary. It is recommended that flumazenil be administered carefully by titration in increments of 0.1 mg.min-1 to avoid emergence reactions by awakening too fast (tachycardia, hypertension). Usually a mean total dose of 0.4-0.5 mg will lead to prompt awakening.

Methohexital vs midazolam/flumazenil anaesthesia during laryngoscopy under jet ventilation.

In a randomised clinical study, two total intravenous anaesthesia techniques for microlaryngoscopic laser surgery were compared. After an induction dose of 100 mg methohexital, Group I received a maintenance infusion of 10 mg.min-1. In Group II anaesthesia was obtained by 15 mg midazolam followed by 0.1 mg.min-1 continuously and terminated by the injection of flumazenil. For analgesia 5 mg alfentanil were administered. Opiate-induced respiratory depression was antagonised by 0.08 to 0.12 mg naloxone. Prior to, during, and after surgery, adrenergic response was assessed by HPLC-analysis of blood taken from a peripheral vein. Haemodynamic responses to the operation and during the post-operative period were almost identical in both groups. In Group I, the mean recovery period of 14 min was significantly longer than in Group II (9 min), where patients received a mean dose of 0.53 mg (+/- 0.15) flumazenil. Resedation could be observed in all patients receiving flumazenil within 60 min after antagonisation, which was associated with a mean decrease in O2-saturation from 95% to 88%. There was no difference in epinephrine and norepinephrine blood levels between the two groups prior to and during anaesthesia. In all patients, arousal was associated with a significant increase in the epinephrine plasma concentration. While blood levels in Group I decreased during the post-operative period to levels prior to surgery, the concentrations in Group II remained elevated. In one patient who received no naloxone, the reversal of midazolam action induced a 16-fold increase in catecholamine levels (from 50 to 800 ng.l-1) associated with a tachycardia of 170 b.min-1 and hypertension of 160 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)