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J Hobbhahn

Publications and source records attributed to J Hobbhahn.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effects of sevoflurane and isoflurane on systemic vascular resistance: use of cardiopulmonary bypass as a study model.

We have examined the dose-related effects of sevoflurane and isoflurane on systemic vascular resistance (SVR) during cardiopulmonary bypass (CPB) in patients undergoing elective coronary artery surgery. Fifty-two patients were allocated randomly to one of six groups to receive 1.0, 2.0 or 3.0 vol% (inspiratory) sevoflurane or 0.6, 1.2 or 1.8 vol% isoflurane, or to a control group. During hypothermic (32-33 degrees C) non-pulsatile CPB, systemic vascular resistance index (SVRI) was recorded before administration of volatile anaesthetics and every 5 min for 20 min. Sevoflurane and isoflurane concentrations were measured next to the gas inlet port and at the gas outlet port of the oxygenator. Wash-in of sevoflurane occurred more rapidly than that of isoflurane, reaching a relatively steady state for both agents from the 10th to the 20th min. There was no significant change in SVRI in patients receiving 1.0 and 2.0 vol% sevoflurane, and 0.6 and 1.2 vol% isoflurane, compared with baseline values. However, 3 vol% sevoflurane decreased SVRI at 10, 15 and 20 min, and 1.8 vol% isoflurane decreased SVRI significantly at 15 and 20 min, whereas SVRI increased at 15 and 20 min in the control group. Thus during CPB, sevoflurane had similar vasodilator effects on SVRI as isoflurane.

Adult↗
PubMed1996

Isoflurane waste gas exposure during general anaesthesia: the laryngeal mask compared with tracheal intubation.

We have compared exposure to isoflurane while using the laryngeal mask airway (LMA) during anaesthesia under positive pressure ventilation with exposure while using tracheal intubation. Trace concentrations of isoflurane were measured directly using a highly sensitive photoacoustic infrared spectrometer (Bruel and Kjaer 1302, Denmark) during general anaesthesia in 20 eye surgery procedures. Measurements were made at six locations (three personnel-related, three leakage-related) in the operating theatre. Despite some high isoflurane values (greater than 2000 ppm at one leakage-related measurement point) all measured values at the personnel-related points were low (the majority were less than isoflurane 2 ppm). In the LMA group, mean trace concentrations were slightly higher than in the tracheal tube (ET) group. Mean exposure to isoflurane, expressed as median (range) related to anaesthetic administration, was highest for the auxiliary nurse (0.64 (0.22-26.89) ppm for the LMA compared with 0.31 (0.02-1.07) ppm for the tracheal tube), followed by the anaesthetist (0.50 (0.28-2.28) ppm for the LMA compared with 0.35 (0.02-0.73) ppm for the tracheal tube) and the surgeon (0.36 (0.20-3.93) ppm for the LMA compared with 0.29 (0.01-0.50) ppm for the tracheal tube). We conclude that the use of the LMA in patients undergoing ventilation is not associated necessarily with high concentrations of isoflurane in a modern working environment.

Anesthesia, Inhalation↗
PubMed1996

Perioperative changes in cardiac autonomic control in patients receiving either general or local anesthesia for ophthalmic surgery.

To investigate whether local (LA) or general anesthesia (GA) provides more perioperative stability in cardiac autonomic tone, we analyzed heart rate variability (HRV) by means of spectral analysis, intraoperatively and up to 3 h postoperatively, in otherwise healthy patients scheduled for cataract surgery. Fourteen patients received GA (premedication: clorazepate; anesthetic induction: propofol, alfentanil, atracurium; anesthetic maintainance: isoflurane, alfentanil; airway management: laryngeal mask airway), and 14 patients received LA (retrobulbar block with bupivacaine/mepivacaine). In the GA group, total power, as an indicator of cardiac autonomic activity, was significantly reduced intraoperatively and increased slowly during the postoperative period. The ratio of low frequency/high frequency (LF/HF) power, indicating cardiac sympathovagal balance, did not change significantly intraoperatively and remained stable in the postoperative period. The LA group showed no significant changes in total power intraoperatively. Postoperatively, heart rate and the LF/HF power ratio were significantly increased in the LA group compared to the GA group. GA as described above was associated with intra- or postoperative stability of the cardiac sympathovagal balance. Thus GA had no disadvantageous effects on the perioperative cardiac autonomic tone during ophthalmic surgical procedures compared to LA in otherwise healthy patients.

Adult↗
PubMed1996

[Occupational exposure in the operating room by isoflurane when using the laryngeal mask].

Success of intraocular surgery depends in part on low intraocular pressure, sufficient muscle relaxation during the operative period, and avoidance of coughing during emergence from anaesthesia. Isoflurane (ISO) guarantees deep anaesthesia and Laryngeal Mask Airway (LM) makes emergence smoother than when using conventional endotracheal intubation. Occupational exposure to isoflurane appears unavoidable near the potential main source of leakage, the "patient's mouth". Due to the short distance between the patient's mouth and the working area, the risk of exposure for the surgeon could be high. Traces of anesthetic gases may cause various negative effects on the health of the personnel. Higher abortion rates are reported on in recent literature. The aim of this study was to quantify trace amounts of ISO and then to compare these values with international threshold limits. In this study, trace concentrations of ISO were measured directly by means of a high sensitive photoacoustic infrared spectrometry analyser. Measurements were done continuously every 120 seconds at the working places of the surgeon, anaesthetist and the assisting nurse. One possible leakage source, the patient's mouth, was also analysed. 10 cataract operations under general anaesthesia were included in the study. All the measured values were low, the majority under 2 ppm isoflurane. The national threshold values (10 ppm) were not exceeded. We conclude that the use of the LMA in ventilated patients is not associated with high concentrations of isoflurane in the working environment of the operating theatre personnel during eye surgery. Trace concentrations of isoflurane using the LMA are comparable with those using ET under these working conditions. Under other working conditions, higher concentrations may be expected should therefore be controlled.

Air Pollutants, Occupational↗
PubMed1996

[Sevoflurane in pediatric anesthesia].

Sevoflurane may be an interesting substance for paediatric anaesthesia due to its combination of a very low blood-gas partition coefficient and non-pungency. This review discusses the status of sevoflurane in paediatric anaesthesia on the basis of studies published so far. The blood-gas partition coefficient of sevoflurane in children is 0.66, and hence markedly lower than those of isoflurane (1.25) and halothane (2.26) [15]. Induction of anaesthesia with sevoflurane/N2O is slightly shorter compared to halothane/N2O (Table 1) [4]. During induction of anaesthesia, sevoflurane/O2 is more often associated with excitement (35%) than sevoflurane/N2O (5%) and halothane/N2O (5%) [25]. Seizure-like movements in one case [1] and electrically generalised but clinically silent seizure activity in two cases [12] may raise the question of seizure-inducing effects of sevoflurane. However, up to now there is no clinical evidence of epileptogenic effects of sevoflurane. The MAC50 in neonates and infants 1-6 months of age is 3.3 vol% [14]; in infants 6-12 months and children 1-12 years of age it is 2.5 vol.% [14]. Sixty per cent N2O decreases the MAC50 of sevoflurane and desflurane by only 20%-25% [3, 14]. In contrast, 60% N2O decreases the MAC50 of halothane in children by 60% [16]. Thus, the MAC-reducing effect of N2O in children appears to be attenuated in the presence of less soluble inhalation anaesthetics. Sevoflurane has a similar low incidence of airway irritation as halothane and provides a smooth induction (Fig. 2) [4]. Haemodynamics during sevoflurane anaesthesia may be somewhat more stable compared to halothane. Serum fluoride levels increase rapidly when sevoflurane is administered, but decrease shortly after discontinuation [4]. Mean maximum levels reported are about 20 mumol/l and are of no concern for renal function. A study with mivacurium indicates more pronounced muscle relaxation by sevoflurane compared to halothane [9]. Sevoflurane may induce malignant hyperthermia. Emergence from sevoflurane anaesthesia is significantly more rapid than after halothane anaesthesia (Table 1); however, it is associated with more restlessness and agitation, probably due to the earlier perception of pain [4]. The incidence of postoperative nausea and vomiting after sevoflurane anaesthesia is comparable to that after halothane (Table 2). Sevoflurane may be a user-friendly alternative to halothane and is more preferred by children than halothane [32]. The status of sevoflurane in paediatric anaesthesia will depend on several factors: its own benefit/risk-ratio, a possible re-evaluation of the known risks of halothane and the financial limitations of the hospitals.

Anesthesia Recovery Period↗
PubMed1996

[Occupational exposure to enflurane and laughing gas in operating rooms].

Current scientific evidence suggests that chronic exposure to trace concentrations of anaesthetic gases may result in various forms of untoward health responses in operating room personnel. Although there are no clear dose-effect-relationships, in Germany threshold values (MAK-values) exist for nitrous oxide of 100 ppm and for enflurane of 20 ppm. Aim of this investigation was, to determine the exposure of the operating room personnel under modern working conditions using a standardized anaesthetic procedure. By means of a direct-reading, high sensitive gas monitor trace concentrations of nitrous oxide and enflurane were measured at three personnel-related (surgeon, anaesthetist, auxiliary nurse) and a potential leakage source (patient's mouth). The calculation and assessment of the measured concentrations followed the prescriptions of the technical rules for hazardous substances 402 and 403 (TRGS 402 and 403). The personnel-related concentrations were clearly under the MAK-values of 100 ppm nitrous oxide and/or 20 ppm enflurane. The time weighted averages were for the personnel-related measurement points, indicated in ppm for nitrous oxide and enflurane, respectively: "surgeon" 28.3/0.25, "anaesthetist" 39.3/0.34 and "auxiliary nurse" 64.6/0.57. At the leakage source "patient's mouth" time weighted averages of 317 ppm nitrous oxide and 3.79 ppm enflurane were measured. Under air-conditioning with a high air change rate, a central scavenging system and low leakage anaesthesia machine low trace concentrations of anaesthetic gases were measured. Despite an average contamination of approx. 300 ppm nitrous oxide at the "patient's mouth" personnel-related values remained clearly under the MAK-values. Outside the mainstream of the air-conditioning system the group "auxiliary nurse" had an approximately 30% higher exposure than the other groups. Under the described conditions, the working environment "operating room" can be classified as a low exposure working area.

Air Pollutants, Occupational↗
PubMed1995

[Nitrous oxide exposure to personnel in a recovery room with modern climate control].

Epidemiologic studies have shown that trace concentrations of inhalation anaesthetics polluting the air of operating theatres could have deleterious effects on the personnel's health. Nitrous oxide (N2O) oxidises vitamin B12 and thus decreases DNA production by inactivation of methionine synthase. Therefore, the United States and most European health authorities recommend threshold values to protect against potential health risks. These values range from 25 to 100 ppm, expressed as time-weighted averages (TWA). There is a lack of data concerning measurements of trace concentrations under defined conditions. The aim of this study was to quantify levels of N2O in a recovery room (RR) with an air conditioning system. METHODS. Trace concentrations of N2O were determined in the main RR of the University Hospital of Regensburg (Germany). Measurements were taken for 5 days from 8:00 a.m. to 8:00 p.m. Trace concentrations of N2O were measured directly by means of a highly sensitive photoacoustic infrared spectrometry analyser. The lower detection limit was 0.03 ppm. Samples of room air were taken continuously from six different places in the recovery room, five of which had a distance of 50 cm to the patients' heads. One point represented the nurses' desk 5 m away from the patients. TWAs were calculated for each day and location. RESULTS. All values were below 5 ppm TWA at each location. Typical TWA (range) values recorded at day 2 were for point 1:3.5 ppm (0.4-8.9), point 2:3.2 (0.5-7.3), point 3:3.0 (0.5-5.4), point 4:3.7 (0.5-21.2), point 5:3.2 (0.6-6.6), and at the nurses' desk 3.3 (0.5-6.3). Peak concentrations of nearly 25 ppm were reached for at least 10 min. Significant differences between the days and locations could not be found (P < 0.05, Wilcoxon test). CONCLUSION. Exposure to N2O in a climatised RR is determined by several factors: (1) efficacy of air conditioning, with 10.7 changes per hour without recirculation; (2) recovery room size; (3) transport of the patients takes about 15 min, during which some quantities of N2O leave the patient; and (4) high numbers of patients staying 2 and more hours in the recovery room and exhaling smaller concentrations of N2O into the room air. Because of these factors, all measured values are significantly below the standard international threshold values. Under other conditions of room design, such as ventilation and size, measured values may be higher.

Air Conditioning↗
PubMed1995

[Severe legionellosis after abuse of anti-inflammatory drugs--diagnostic and intensive care aspects based on a case report].

Legionella infections are getting increasingly important as causes of severe pneumonias or of acute respiratory insufficiency. Consumptive or immunosuppressive underlying diseases such as diabetes mellitus, cardiac insufficiency, alcohol-induced liver damage, malignant tumours or drug-induced immunosuppression after organ transplantation, are among the risk factors. Diagnosis is based on direct identification of the pathogen from body secretions by means of direct immunofluorescence. The serological immunoresponse often takes place long after outbreak of the disease or fails entirely to appear and is therefore only suitable for retrospective confirmation. Therapy of choice is an intravenous administration of erythromycin. There are now increasing pointers to the efficiency of fluoroquinolone antibiotics, such as ciprofloxacin. We report on the course of a severe case of legionnaire's disease with multiple organ failure occurring in a patient after bone marrow depression induced by anti-inflammatory drugs. Treatment erythromycin resulted in a marked cholestasis, so that antibiotic treatment was changed to ciprofloxacin. This therapy as well as the supportive intensive-care treatment eventually led to the patient's complete recovery. Based on the case report, fundamental aspects of diagnostics, antibiotic treatment, intensive-care treatment and prognosis of severe cases of legionellosis are discussed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

[Rates of awakening, circulatory parameters and side-effects with sevoflurane and enflurane. An open, randomized, comparative phase III study].

OBJECTIVE: Sevoflurane is a "new" volatile inhaled anaesthetic currently undergoing phase III clinical trials in Europe and USA. Owing to the low blood solubility, rapid induction of anaesthesia and emergence from anaesthesia would be expected. In this study, we compared emergence times and haemodynamics in patients receiving either sevoflurane or enflurane. Furthermore, all adverse experiences were recorded, and the relationship to the drug administered was rated. METHODS: Thirty ASA physical status I and II patients were studied in an open, prospective and randomised clinical trial. Anaesthesia was induced with fentanyl, thiopentone and vecuronium for facilitating endotracheal intubation. Anaesthesia was maintained with sevoflurane or enflurane, 60% nitrous oxide in oxygen and additional doses of fentanyl (1-2 micrograms/kg/h). ECG, blood pressure (non-invasive), inspiratory and end-tidal concentrations of sevoflurane or enflurane were monitored continuously. At the end of surgery, administration of sevoflurane or enflurane and nitrous oxide stopped without tapering and emergence times were recorded. All adverse experiences which occurred until the third postoperative day were recorded and the relationship to the inhaled anaesthetic was rated as "none", "unlikely", "possible", "probable" or "highly probable". RESULTS: With the exception of the end-tidal concentration at the end of surgery and the mean inspiratory and end-tidal concentrations, which were higher for sevoflurane, the two patient groups were comparable. Pulmonary elimination was significantly faster and emergence time was significantly shorter (5 vs. 9 minutes) with sevoflurane. Emergence time did not correlate with the duration of anaesthetic exposure (MAC hours) for sevoflurane. There was no difference in the time courses of heart rate and mean arterial blood pressure between sevoflurane and enflurane. No adverse experiences with a "probable" or "highly probable" relationship to the inhaled anaesthetic were observed. CONCLUSION: Emergence time after inhalation anaesthesia depends on (alveolar) ventilation, blood-gas solubility coefficient and, at least for enflurane and isoflurane, on the dose applied (MAC hours). There is no positive correlation between emergence time and dose applied for sevoflurane. Due to the lower blood-gas solubility coefficient (0.6-0.7 for sevoflurane vs. 1.8 for enflurane) pulmonary elimination is faster and emergence time is shorter with sevoflurane. Supplementing inhalation anaesthesia with fentanyl, there is no difference in the time courses of heart rate and mean arterial blood pressure between sevoflurane and enflurane.

Adult↗
PubMed1995

[Exposure of intensive care personnel to isoflurane in long-term sedation].

OBJECTIVE: Isoflurane is a suitable agent to produce sedation in the intensive care unit (ICU). However, data concerning occupational exposure to isoflurane during long-term sedation are not yet available. The purpose of this study was to evaluate occupational exposure to isoflurane in the ICU. DESIGN: Trace concentrations of isoflurane were measured directly by means of photoacustic infrared spectrometry during isoflurane sedation in ten cases over a period of 24 hours. Values were obtained at four personnel-related and two leakage-related locations in an ICU chamber. RESULTS: All measured values were low, the majority under 3 ppm isoflurane at the personnel-related points. Peak concentrations up to 40 ppm were recorded for several minutes during nursing interventions. At measurement point "nearby patient's mouth" values up to 5 ppm were recorded, at location "anaesthesia machine" values ranged from 2 to 69 ppm isoflurane. CONCLUSION: We conclude that an effective high flow scavenging system, a low-leakage anaesthesia machine and an airconditioning equipment without recirculation could keep occupational exposure low. The majority of the measured values was below the NIOSH recommendation (2 ppm). All values was lower than a national state recommendation (10 ppm). Under other circumstances (e.g. without scavenging system) air pollution will be higher and therefore measurements at the working place are needed.

Air Pollutants, Occupational↗
PubMed1995

[Nitrous oxide exposure of operating room personnel in intubation anesthesia].

INTRODUCTION: Epidemiological studies have shown that trace concentrations of inhalation anaesthetics polluting the air of operation theatre could have adverse effects on the personnel's health. Nitrous oxide (N2O) oxidizes vitamin B12 and thus decreases DNA production by inactivation of methionine synthase. Therefore, US and most European health authorities recommend threshold values to protect against potential health risks. These values range from 25 ppm to 100 ppm, expressed as time-weighted averages (TWA). There is a lack of data concerning measurements of trace concentrations under defined conditions. The aim of this study was to quantify levels of N2O in an operating theatre (OT) under modern working environment conditions. METHODS: Trace concentrations of N2O were determined in the OT at three personnel-related and three potential leakage related points and TWA's were calculated. Trace concentrations of N2O were measured directly by means of a highly sensitive photoacoustic infrared spectrometry analyser. The lower detection limit was 0.03 ppm. RESULTS: Values were below 100 ppm TWA at personnel-related locations. NIOSH 25 ppm threshold limit value was exceeded several times. Significant differences between location surgeon and anaesthetist and auxiliary nurse were detected (p < 0.05, Wilcoxon test). CONCLUSION: Exposure to N2O in a climatised OT is determined by several factors: 1. Efficacy of the air-conditioning with 20 changes per hour without recirculation, 2. OT size, 3. low leakage anaesthesia machine, and 4. avoidance of intermittent nitrous oxide supply during induction. Due to these factors, most measured values are below threshold values. In case of other concepts of room design such as ventilation and size, measured values may be higher.

Adult↗
PubMed1994

[Emergence times, hemodynamics and adverse effects of sevoflurane and isoflurane: an open, randomized, comparative phase iii study].

Sevoflurane is a "new" volatile inhaled anaesthetic that is currently undergoing phase III clinical trial in Europe and the United States. Owing to the low blood solubility, rapid induction of anaesthesia and emergence from anaesthesia would be expected. In this study, we compared emergence times and haemodynamics in patients receiving either sevoflurane or isoflurane. Furthermore, all adverse effects were recorded and the relationship to the drug administered was rated. METHODS. Fifty ASA physical status I and II patients were studied in an open, prospective, randomised clinical trial. Anaesthesia was induced with fentanyl, thiopentone, and vecuronium for facilitating endotracheal intubation and maintained with sevoflurane or isoflurane, 60% nitrous oxide (N2O) in oxygen (O2), and additional doses of fentanyl (1-2 micrograms/kg.h). The electrocardiogram, blood pressure (non-invasive), O2 saturation, temperature, and end-tidal concentrations of sevoflurane or isoflurane, N2O, and carbon dioxide were monitored continuously. At the end of surgery, administration of sevoflurane or isoflurane and N2O was discontinued without tapering and emergence times were recorded. All adverse events that occurred until the 3rd postoperative day were recorded and the relationship to the inhaled anaesthetic was rated as "none", "unlikely", "possible", "probable", or "highly probable". RESULTS. With the exception of gender, the two patient groups were comparable (Tables 1 and 2). Due to the higher MAC value, mean end-tidal concentrations were higher for sevoflurane (0.82% vs. 0.59% for isoflurane). The duration of anaesthetic exposure was 1.3 MAC h (calculation with FIO2 = 1.0 MAC value) and 3.1 MAC h (calculation with FIO2 = 0.4 in N2O MAC value), respectively, for both inhaled anaesthetics. Pulmonary elimination was faster (Fig. 1) and emergence time shorter (7 min vs. 11.5 min, Table 3) with sevoflurane. There was no difference in the time courses of heart rate and mean arterial blood pressure (Figs. 2 and 3). No adverse effects with a "probable" or "highly probable" relationship to the inhaled anaesthetic were observed. Table 4 shows the adverse events with a possible relationship to the drug administered. Further evaluations of nausea, vomiting, and dizziness are shown in Table 5. DISCUSSION. Emergence time after inhalation anaesthesia depends on pulmonary elimination and MACawake, that is, the end-tidal concentration that would allow opening of the eyes on verbal command. Pulmonary elimination depends on dose applied (MAC h), alveolar ventilation, and blood-gas solubility coefficient. Due to the lower blood-gas solubility coefficient (0.6-0.7 for sevoflurane vs. 1.3-1.4 for isoflurane) and in accordance with the investigations of Frink et al. [4] and Smith et al. [16], emergence time was significantly shorter with sevoflurane. Gender, the only difference between the two patient groups, does not influence pulmonary elimination and MACawake [8]. Supplementing inhalation anaesthesia with fentanyl, there was no difference in the time courses of heart rate and mean arterial blood pressure between sevoflurane and isoflurane. Adverse events with a possible relationship to the inhaled anaesthetic occurred in both groups.

Adult↗
PubMed1991

Left ventricular surface tissue oxygen pressures determined by oxygen sensitive multiwire electrodes in pigs.

STUDY OBJECTIVE: Polarographic oxygen sensitive electrodes can be used to measure tissue oxygen pressures on the surface of the beating heart. The purpose of the study was to clarify the significance of these PO2 determinations. DESIGN: Changes in left ventricular surface oxygen pressures, subendocardial or subepicardial wall functions (ultrasonic dimension technique), and blood flow (radioactive microsphere technique) were correlated during different degrees of acute coronary artery stenoses in pigs. EXPERIMENTAL MATERIAL: 19 anaesthetised open chest pigs, 28-40 kg body weight, were studied during different degrees of constriction of the left anterior descending artery which did not influence overall left ventricular function or irreversibly damage the myocardium. MEASUREMENTS AND MAIN RESULTS: Highly significant (p less than 0.001) correlations (each % delta) were obtained for surface tissue oxygen pressures (y) with subepicardial (y = 0.002 e 0.10x; r = 0.89) and subendocardial (y = 1.44 e 0.04x; r = 0.98) blood flow values, as well as with subendocardial function (y = 82.4 + 0.22x; r = 0.89); a significant correlation was also obtained for subendocardial function (y) with subendocardial blood flow (y = 66.0 + 0.28x; r = 0.69). However, no significant correlation was obtained for polarographic tissue PO2 with subepicardial segment function, indicating that regional function was maintained when tissue PO2 recordings were not much above 0 kPa and when blood flow was reduced by 25 to 30%. CONCLUSIONS: Oxygen pressures of the superficial layers of the left ventricle are relatively high at normal values of oxygen consumption but decrease rapidly if blood supply is reduced. Regional wall function is preserved at low oxygen pressures. Polarographic surface PO2 electrodes hence can be used to study influences of experimental interventions on oxygenation of the normally perfused and of the moderately ischaemic myocardium.

Animals↗
PubMed1991

Heparin reversal by protamine in humans--complement, prostaglandins, blood cells, and hemodynamics.

Fourteen noncardiac surgical patients received heparin (10,000 IU), which was neutralized by 100 mg protamine injected within 2 min during steady-state anesthesia. After protamine application, plasma complement C3a, thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and KH2PGF2 alpha increased significantly, whereas prostacyclin (6-keto-PGF2 alpha) levels did not change. This mediator response was associated with transient leukopenia and thrombocytopenia. Arterial pressure, pulmonary arterial pressure, and transpulmonary pressure gradient increased significantly. Heart rate, cardiac output, pulmonary capillary wedge pressure, and arterial PO2 remained constant. Positive correlations of plasma C3a were observed with pulmonary leukosequestration and plasma TxB2. Inverse correlations of C3a were noted with the counts of leukocytes and of platelets. A positive correlation was found between TxB2 and pulmonary arterial pressure. Our results indicate that marked activation of the complement system and the cyclooxygenase pathway is common after heparin reversal by protamine in anesthetized patients. This is in contrast to previous human studies performed after cardiopulmonary bypass but agrees well with results obtained in animal experiments. The mediator response in our patients, however, was not accompanied by hemodynamic instability, suggesting appropriate compensatory mechanisms.

Aged↗
PubMed1991

[Complications caused by protamine. 1: Pharmacology and pathophysiology].

Protamine is a strongly alkaline polypeptide with a molecular weight of about 4500. Protamine solutions contain paraben compounds as antimicrobial agents. Rapid neutralization of heparin by protamine may cause an anaphylactoid reaction characterized by a non-immunogenic histamine release and by unknown mediators mechanisms. This response is associated with systemic peripheral vasodilation resulting in slight to moderate hypotension. Weak negative inotropic effects by mechanisms different from the reduction of ionized calcium concentrations may also contribute to systemic hypotension. Apart from these mostly slight reactions, severe reactions may occur with life-threatening systemic hypotension, bronchospasm and, in rare cases, death. They are caused by anaphylactic/anaphylactoid reactions resulting in catastrophic pulmonary vasoconstriction which induces right and eventually global ventricular failure. Sensitization to protamine (anaphylactic) and anaphylactoid reactions are the underlying mechanisms. The majority of anaphylactic/anaphylactoid reactions are associated with complement activation and the release of anaphylatoxins C3a and C5a. These activate the cyclo-oxygenase pathway of the arachidonic acid metabolism in yet unidentified cells, probably within the lung. As a result, thromboxane and prostaglandins are released. Thromboxane is the pivotal mediator responsible for the pulmonary vasoconstriction and, presumably, also for the bronchospasm during protamine reactions. The pronounced activation of polymorphonuclear leukocytes and the decrease in platelet counts may reflect a mere epiphenomenon. The degree of right ventricular afterload increase at which systemic hypotension requiring immediate therapy would occur depends mainly on the contractile state of the heart. Potential risk patients for severe protamine reactions are depot insulin-dependent diabetics and patients with prior exposure to protamine.

Anaphylaxis↗
PubMed1991

[Complications caused by protamine. 2. Therapy and prevention].

Treatment of reactions. The treatment of reactions to protamine is still symptomatic. Hypotension resulting from systemic vasodilation (anaphylactoid reaction) is treated by volume infusion, and alpha-stimulating catecholamines may be necessary. The combination of increased right ventricular afterload and systemic hypotension (anaphylactic/anaphylactoid reaction) requires primarily the improvement of coronary perfusion pressure and, thus, of O2 delivery to the right ventricular myocardium. To this end, catecholamines with alpha-stimulating action should be administered. Nitroglycerin is indicated when pulmonary hypertension persists in the presence of essentially normal systemic pressure. In the acute situation, steroids and antihistamines have no beneficial effect. Prevention of protamine reactions. For prevention of systemic hypotension by vasodilatation, protamine should be infused very slowly and not during hypovolemia. General prophylaxis using H1/H2 antagonists is not justified. Reliable preoperative identification of patients who would suffer an anaphylactic/anaphylactoid reaction to protamine, for example by skin tests or by measuring specific anti-protamine IgE or IgG antibodies, is not possible. This prevents individual prophylaxis in risk patients. In view of the low incidence of severe protamine reactions and the lack of better alternatives to the heparin/protamine regimen, general prevention is not indicated. For patients who are potentially at risk (insulin-dependent diabetics, prior protamine exposure), the side-effects of preventive measures must be weighed against their benefits. Only known sensitivity to protamine justifies certain preventive actions. In vascular surgery prostacyclin can be used instead of heparin/protamine or can be withheld (fading out of heparin action). Administration of steroids and/or antihistamines should be avoided. In cardiac surgery the use of hexadimethrine (if available) or total avoidance of protamine is paramount. Corticosteroids may be considered. Aortic administration of protamine and anticoagulation with ancrod are not recommended. The most promising compounds for rpharmacologic prevention of anaphylactic/anaphylactoid reactions in the future are thromboxane receptor antagonists.

Anaphylaxis↗