Andrea Michalek-Sauberer

Effect of prostacyclin on platelets, polymorphonuclear cells, and heterotypic cell aggregation during hemofiltration*

ObjectivesHemodialysis activates both platelets and leukocytes, which play a role in the development of multiple organ dysfunctions in critically ill patients. Prostacyclin inhibits both cell types in vitro. To examine the hypothesis that prostacyclin prevents cellular activation during clinical hemofiltration, we investigated the expression of activation markers on platelets and leukocytes using whole blood flow cytometry. DesignProspective, randomized, double-blind, controlled trial. SettingIntensive care unit. PatientsA total of 24 consecutive, critically ill, mechanically ventilated patients with acute renal failure secondary to sepsis or major surgery. InterventionsFor anticoagulation during hemofiltration, patients received either unfractionated heparin or unfractionated heparin and prostacyclin (5 ng·kg−1·min−1). Anticoagulants were administered into the extracorporeal circuit before the hemofilter. Blood samples were obtained from an arterial catheter before hemofiltration and from the inlet and outlet lines of the extracorporeal circuit at 1 and 24 hrs during hemofiltration. Measurements and Main ResultsExpression of GP IIb–IIIa and P-selectin on adenosine diphosphate-activated platelets and platelet-leukocyte aggregation were significantly lower after the passage of blood through the hemofilter in patients receiving an extracorporeal infusion of prostacyclin plus heparin when compared with control patients receiving heparin only. There were no statistically significant differences in the expression of CD11b on leukocytes between the two groups. ConclusionsThese findings suggest that prostacyclin reversibly inhibits platelet function by diminishing the expression of platelet fibrinogen receptors and P-selectin and reduces heterotypic platelet-leukocyte aggregation during clinical hemofiltration. However, prostacyclin fails to inhibit leukocyte activation at clinically relevant doses.

The cerebral and cardiovascular effects of cisatracurium and atracurium in neurosurgical patients.

Drugs for neurosurgical patients should not increase intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow.This double-blind, cross-over study compares the effects of a single (3 x effective dose producing 95% twitch depression) intravenous bolus dose of cisatracurium 0.15 mg/kg with atracurium 0.75 mg/kg on mean red blood cell flow velocity in the middle cerebral artery (CBFV; transcranial Doppler), ICP (intraventricular or intraparenchymal monitor), mean arterial pressure (MAP), CPP (MAP - ICP), and heart rate (HR) every minute during a 15-min study period. Included in the study were 14 sedated and ventilated adult neurosurgical patients. After the cisatracurium bolus, ICP, CPP, CBFV, MAP, and HR did not change, and no histamine related events were observed. After the atracurium bolus, ICP, CPP, CBFV, and MAP decreased. The lowest values of ICP (-16% of baseline), CPP (-5%), CBFV (-8%), and MAP (-7%) were recorded 2-4 min after the atracurium bolus injection. After this transient decrease, MAP and CPP returned to baseline, whereas CBFV and ICP transiently exceeded baseline values. The highest values of CBFV (5%) and ICP (17%) were recorded 9-12 min after the atracurium bolus injection. Five patients showed a typical histamine response after atracurium, with a decrease in MAP and flushing. Excluding these five patients eliminated statistical significance in ICP, CPP, CBFV, and MAP differences. In conclusion, cisatracurium demonstrated fewer cerebral and cardiovascular hemodynamic side effects in sedated adult neurosurgical patients. Implications: This double-blind study in sedated and mechanically ventilated adult neurosurgical patients demonstrates that an intravenous bolus dose of the neuromuscular blocker cisatracurium results in less cerebral (intracranial pressure, cerebral perfusion pressure, middle cerebral artery blood flow velocity) and cardiovascular (blood pressure) hemodynamic side effects, compared with an equipotent dose of atracurium.

Perioperative Auricular Electroacupuncture Has No Effect on Pain and Analgesic Consumption After Third Molar Tooth Extraction

BACKGROUND:Auricular acupuncture (AA) has been shown to alleviate acute and chronic pain. We investigated the effects of auricular electroacupuncture (AE) on pain and analgesic drug consumption in the first 48 h after unilateral mandibular third molar tooth extraction under local anesthesia in a prospective, randomized, double-blind, placebo-controlled study in 149 patients. METHODS:Patients received either AA with electrical stimulation (AE, n = 76) or without (AA, n = 37) electrical stimulation at an alternating frequency of 2/100 Hz or a sham AE with metal plates instead of needles and no electrical stimulation, no-needle (NN, n = 36) at the AA points 1 (tooth), 55 (Shen men) and 84 (mouth) during the entire study period. Regularly rated pain intensity (five-point verbal rating scale), consumption of acetaminophen 500 mg tablets and additional rescue medication with mefenamic acid 500 mg were assessed. RESULTS:The median fraction of time when pain was rated as moderate or worse (upper and lower quartile): AE: 33% (12%, 64%), AA: 22% (6%, 56%), NN: 30% (7%, 53%) did not differ significantly among the treatment groups. There were no significant differences in mean number of acetaminophen 500 mg tablets (range): AE: 5.2 (0–12), AA: 4.6 (0–11), NN: 5.4 (0–10) or percentage of patients requiring additional mefenamic acid: AE: 19%, AA: 18%, NN: 19%. CONCLUSION:We conclude that neither AE nor AA alone reduce either pain intensity or analgesic consumption in a molar tooth extraction model of acute pain.

P-Stim™ auricular electroacupuncture stimulation device for pain relief

Acupuncture is now accepted as a complementary analgesic treatment. Auricular acupuncture is a distinct form of acupuncture. Electrical stimulation of acupoints (electroacupuncture) increases the effects of acupuncture. Recently, an auricular electroacupuncture device, the P-Stim™, has become available. Clinical studies in outpatients have investigated the P-Stim in chronic musculoskeletal pain and its use for minor surgery. In chronic cervical or low back pain, auricular electroacupuncture was more effective than conventional auricular acupuncture. The results in acute pain were controversial. Auricular electroacupuncture reduced pain and remifentanil consumption during oocyte aspiration when compared with conventional auricular acupuncture or a sham treatment. However, after third molar tooth extraction, auricular electroacupuncture and auricular acupuncture failed to reduce either postoperative pain or analgesic consumption. Further large-scale studies are required to evaluate the analgesic efficacy of auricular electroacupuncture.

A case of suspected malignant hyperthermia during desflurane administration.

A 13-yr-old boy (47 kg) presented for cerebral angiography after embolization of an arteriovenous malformation. Since 1994, the boy had undergone at least three surgical interventions for his arteriovenous malformation under general anesthesia in our university hospital (anesthetic drug unknown due to missing records). There was no known family history of malignant hyperthermia or muscle disease. Fifteen minutes after premeditation with 2 mg midazolam intravenously (IV), anesthesia was induced with 0.1 mg fentanyl, 50 mg propofol, and 4 mg vecuronium IV. The trachea was intubated, and controlled ventilation was initiated using a circle anesthesia system with a soda lime CO, absorber. Anesthesia was maintained with desflurane 3% in nitrous oxide (65%)/oxygen (35%) at a flow of approximately 2 L/min and 1 L/min, respectively. Usual monitors were used. Baseline heart rate was 55 bpm, peripheral oxygen saturation (Sao,) 98%, end-tidal CO, (etC0,) 29 mm Hg, and bladder temperature 36.1”C. Due to a technical fault of the fluoroscopy unit, the duration of the procedure was unexpectedly prolonged. After 90 min of desflurane administration, vigorous inspiratory efforts were noted. Ventilation was then controlled manually. The patient’s respiratory rate increased, and despite manual assistance and increased minute ventilation, etC0, continued to increase to a maximum of 85 mm Hg at 100 min of desflurane anesthesia. No pattern suggestive of rebreathing or obstruction was observed in the etC0, wave form, and there were no signs of exhaustion of the CO, absorber. Bladder temperature increased to 37.8”C and profuse sweating was noted. Arterial blood pressure remained stable, but heart rate increased to

The effects of auricular electroacupuncture on obesity in female patients – A prospective randomized placebo-controlled pilot study

BACKGROUND Obesity is a chronic condition related to serious morbidity and mortality of increasing incidence and prevalence. Several studies show a significantly higher weight loss with acupuncture treatment. This is the first prospective, randomized, double-blinded study, testing the effects of auricular electroacupuncture on weight loss in obese female patients. METHODS 56 female obese patients (age>18, Body Mass Index, BMI>25) were randomized to receive either auricular acupuncture with electrical stimulation with a P-Stim® device (verum group, n=28) or placebo treatment with a P-Stim® dummy (n=28) for four days. Three auricular acupuncture points were chosen (hunger 18, stomach 87 and colon 91). The treatment was performed once a week for a period of six weeks. A follow-up visit was performed after 4 weeks. At each visit body weight, BMI (Body Mass Index) and body fat were measured. RESULTS Relative reduction of body weight was significantly greater in the verum group (-3.73%; CI=-4.70 to -2.76) than in the placebo group (-0.70%; CI=-1.57 to +0.16; p<0.001) In addition we also observed a significant reduction of BMI (p<0.001) in the verum group (-3.62%; CI=-4.39 to -2.84) compared to placebo (-0.82%; CI=-1.55 to -0.10; p<0.001). No patient reported side effects related to acupuncture. CONCLUSION In conclusion electrical auricular acupuncture could be a safe, additive, non-pharmacological treatment in obese patients.

Novel double and single ryanodine receptor 1 variants in two Austrian malignant hyperthermia families.

BACKGROUND: Malignant hyperthermia (MH) is a potentially lethal genetic disorder in response to volatile anesthetics and depolarizing muscle relaxants. To support the claim that a novel genetic variant causes MH, it is necessary to demonstrate that it has significant effects on the sensitivity of the ryanodine receptor (RYR1) calcium channel. In this study we focused on 2 Austrian families with strong MH disposition and new RYR1 variants. METHODS: We sequenced the entire coding region of the RYR1 from 2 Austrian MH individuals. Genotype–phenotype segregation and evolutionary conservation of the variants were considered. On a functional level, Ca2+ release experiments with fura-2-acetoxymethyl ester were performed in cultured skeletal muscle cells derived from individuals carrying the new variants and compared with control cells from nonsusceptible individuals. Caffeine, 4-chloro-m-cresole (4-CmC), and halothane were used as specific Ca2+ releasing agents. RESULTS: The variant p.A612P in family A segregated with an MH-susceptible phenotype and cells showed an increased sensitivity for all Ca2+-releasing substances tested. In family B, 2 variants (p.R2458H/p.R3348C) were identified. While p.R2458H and p.R2458H/p.R3348C segregated with an MH-susceptible diagnosis, p.R3348C alone showed an MH equivocal diagnosis. Ca2+-release experiments showed that exchanges of these highly conserved amino acids increased the sensitivities for the substances tested (except 4-CmC with p.R2458H and p.R3348C) when compared with the MH-negative control group. CONCLUSIONS: Our results suggest that these variants are new causative MH variants.

3,5-Di-t-butyl catechol is a potent human ryanodine receptor 1 activator, not suitable for the diagnosis of malignant hyperthermia susceptibility

3,5-Di-t-butyl catechol (DTCAT) releases Ca(2+) from rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Hence, it is a candidate for use as a substitute for halothane or caffeine in the in vitro contracture test for the diagnosis of susceptibility to malignant hyperthermia (MH). To characterize the effect of DTCAT at cell level, Ca(2+) release experiments were performed on cultured, human skeletal muscle myotubes using the fluorescent Ca(2+) indicator fura2-AM. DTCAT was also assayed in the in vitro contracture test on human skeletal muscle bundles obtained from individuals diagnosed susceptible (MHS), normal (MHN) or equivocal for halothane (MHEH) and compared to the standard test substances caffeine and halothane. DTCAT increased, in a concentration-dependent manner and with a higher efficacy as compared to caffeine, the free, intracellular Ca(2+) levels of cultured MHN and MHS skeletal muscle myotubes. This effect was similar in both types of myotubes and involved the release of Ca(2+) from SR stores as well as Ca(2+)-influx from the extracellular space. Inhibition of ryanodine receptors either with ryanodine or with ruthenium red markedly reduced DTCAT-induced increase in intracellular Ca(2+) concentration while abolishing that induced by caffeine. In MHN skeletal muscle bundles, DTCAT induced contractures with an EC(50) value of 160 ± 91 μM. However, the sensitivity of MHS or MHEH muscles to DTCAT was similar to that of MHN muscles. In conclusion, DTCAT is not suitable for the diagnosis of MH susceptibility due to its failure to discriminate between MHN and MHS muscles.

3,5-Di-t-butyl catechol (DTCAT) as an activator of the human skeletal muscle ryanodine receptor Ca2+ channel and its evaluation as a test substance for the assessment of susceptibility to malignant hyperthermia

3,5-Di-t-butyl catechol (DTCAT) has been shown to release Ca2+ from rat skeletal muscle sarcoplasmic reticulum (SR) vesicles, which makes it a possible candidate for use as a substitute for halothane or caffeine in the in vitro contracture test (IVCT) for the assessment of susceptibility to malignant hyperthermia (MHS).