Johann Motsch

Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial

BACKGROUND During cardiopulmonary resuscitation (CPR), thrombolysis can help to stabilise patients with pulmonary embolism and myocardial infarction. Moreover, thrombolysis during CPR has beneficial effects on cerebral reperfusion after cardiac arrest. We investigated this new therapeutic approach in patients in whom conventional CPR had been unsuccessful. METHODS We assessed, in a prospective study, patients undergoing CPR after out-of-hospital cardiac arrest for cardiological reasons in whom return of spontaneous circulation was not achieved within 15 min. According to the Ustein criteria, our control group consisted of patients who were assessed during 1 year. After this year patients were treated with a bolus of 5000 U of heparin and 50mg, over 2 min, of tissue-type plasminogen activator (rt-PA treated group). This intervention was repeated if return of spontaneous circulation was not achieved within the following 30 min. For controls only CPR was given. FINDINGS Overall, 90 patients were included; heparin and rt-PA were given to 40 patients. There were no bleeding complications related to the CPR procedures. Of the rt-PA group, 68% (27) had return of spontaneous circulation and 58% (23) were admitted to a cardiac intensive care unit, compared with 44% (22; p=0.026) and 30% (15; p=0.009) of the controls, respectively. At 24 h after cardiac arrest a larger proportion of the rt-PA group than of the controls was alive (35% [14] vs 22% [11], p=0.171), and 15% (six) of rt-PA-treated patients and 8% (four) of controls could be discharged from hospital. INTERPRETATION After initially unsuccessful out-of-hospital CPR, thrombolytic therapy combined with heparin is safe and might improve patient outcome. On the basis of our data a randomised controlled trial might be regarded as ethical.

Stereotactic single-dose radiotherapy of stage I non–small-cell lung cancer (NSCLC)

PURPOSE The treatment of early-stage lung cancers is a primary domain of thoracic surgery, leading to persuasive results. In patients with medical contraindications, radiotherapy is an alternative, although with considerably worse outcome. Radiotherapy is associated with the risk of severe acute side effects and a permanent decrease of lung function. By the introduction of an extracranial stereotactic treatment technique, the amount of normal tissue in the high-dose region can be reduced, allowing the performance of single-dose treatment with high, biologically effective doses. METHODS AND MATERIALS Between October 1998 and May 2001, 10 patients with histologically confirmed Stage I non-small-cell lung cancer were treated with stereotactic single-dose radiotherapy. A self-developed stereotactic frame was used for patient positioning and navigation. Total doses applied ranged from 19 to 26 Gy. After treatment, regular CT-based follow-up was performed. RESULTS During a median follow-up period of 14.9 months, the tumors in 8 of 10 patients were locally controlled. The actuarial overall survival was 80% and 64%, respectively, 12 and 24 months after therapy. Actuarial local recurrence-free survival reached 88.9% and 71.1%, respectively. Therapy-related perifocal normal-tissue reaction occurred in 70% of all treated patients, although no major clinical symptoms were seen. In 5 patients, systemic metastases were found during follow-up; 1 patient developed suspect mediastinal lymph nodes. CONCLUSION Stereotactic single-fraction radiotherapy is a feasible, safe, and effective procedure for the treatment of Stage I non-small-cell lung cancer. It promises high local control with a reduced overall treatment time. However, further investigation in a larger patient collective with extended follow-up is necessary.

Efficacy of ultrasound imaging in obstetric epidural anesthesia

STUDY OBJECTIVE To assess the clinical use of ultrasonographic localization of the epidural space, and to evaluate the clinical efficacy of ultrasound diagnostics in obstetric anesthesia. DESIGN Randomized prospective study. SETTING University Clinic of Obstetrics and Gynecology. PATIENTS 300 parturients, 85 of whom had conventional delivery and 65 who underwent cesarean section. INTERVENTIONS Patients underwent ultrasonography for the identification of the intervertebral structures. Puncture depth and angle were measured to improve the placement of the Tuohy needle. MEASUREMENTS In the ultrasound group, additional puncture data, optimized puncture point, expected puncture depth, and angle were used to optimize the puncture technique. To control for side effects, we compiled data on the number of puncture attempts and the number of necessary puncture levels, visual analog scale (VAS) scores, the rate of side effects, and the patient acceptance of the technique. MAIN RESULTS The two groups were similar regarding demographic data. Using ultrasound for structure detection, the rate of puncture attempts were significantly (p < 0.013) reduced from 2.18 +/- 1.07 to 1.35 +/- 0.61. The mean rate of necessary puncture levels was 1.30 +/- 0.55 and with ultrasound detection 1.136 +/- 0.36 (p < 0.029). Complete analgesia was achieved in 147 patients with ultrasound detection versus 138 patients in the Control group (p < 0,03). The maximum VAS pain score in the control group was 1.3 +/- 2.1 versus 0.8 +/- 1.5 in the Ultrasound group (p < 0.006). The rate of side effects were reduced significantly: 99 patients in the Control group had no side effects compared with 120 patients from the Ultrasound group who were free of side effects. Patient acceptance of the technique in the Ultrasound group was significantly higher than in the Control group. CONCLUSION The clinical use of ultrasound for epidural catheter placement may improve regional anesthesia. The use of ultrasound resulted in superior quality in all measured endpoints.

Astroglial Protein S-100 Is an Early and Sensitive Marker of Hypoxic Brain Damage and Outcome After Cardiac Arrest in Humans

Background—The results of early conventional tests do not correlate with cerebral outcome after cardiac arrest. We investigated the serum levels of astroglial protein S-100 as an early marker of brain damage and outcome after cardiac arrest. Methods and Results—In 66 patients undergoing cardiopulmonary resuscitation after nontraumatic cardiac arrest, blood samples for the evaluation of S-100 were drawn immediately after and 15, 30, 45, and 60 minutes; 2, 8, 24, 48, and 72 hours; and 7 days after initiation of cardiopulmonary resuscitation. Moreover, the serum levels of neuron-specific enolase were determined between 2 hours and 7 days. If patients survived for >48 hours, brain damage was assessed by a combination of neurological, cranial CT, and electrophysiological examinations. Overall, 343 blood samples were taken for the determination of S-100. Maximum S-100 levels within 2 hours after cardiac arrest were significantly higher in patients with documented brain damage (survivors and nonsurvivors, 3.70±0.77 &mgr;g/L) than in patients without brain damage (0.90±0.29 &mgr;g/L). Significant differences between these 2 groups were observed from 30 minutes until 7 days after cardiac arrest. In addition, the positive predictive value of the S-100 test at 24 hours for fatal outcome within 14 days was 87%, and the negative predictive value was 100% (P <0.001). With regard to neuron-specific enolase, significant differences between patients with documented brain damage and those with no brain damage were found at 24, 48, and 72 hours and 7 days. Conclusions—Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and short-term outcome after cardiac arrest in humans.

Ultrasound imaging improves learning curves in obstetric epidural anesthesia: a preliminary study.

PurposeEpidural anesthesia may be difficult in pregnancy. We intended to evaluate the teaching possibilities of ultrasonography as a diagnostic approach to the epidural region.MethodsTwo groups of residents performed their first 60 obstetric epidurals under supervision. One proceeded in the conventional way using the loss of resistance technique (control group = CG). The other group proceeded in the same way but was supported by prepuncture ultrasound imaging, giving them information about the optimal puncture point, depth and angle (ultrasound group = UG). Success was defined as adequate epidural anesthesia requiring a maximum of three attempts, reaching a visual analogue scale score of less than I, while neither changing the anesthesia technique, nor starting at another vertebral level. In addition, intervention by the supervisor was defined as failure.ResultsIn the CG we observed asuccess rate of 60% ± 16% after the first ten attempts followed by a nearly continuous rise of the learning curve. Within the next 50 epidurals the rate of success increased to 84%. In the UG the rate of success started at 86% ± 15%. Wthin 50 epidural insertions it rose up to a level of 94%. The difference between the two groups remained significant (P < 0.001).ConclusionUsing ultrasound imaging for teaching epidural anesthesia in obstetrics we found a higher rate of success during the first 60 attempts compared to conventional teaching. We believe this shows the possible value of ultrasound imaging for teaching and learning obstetric regional anesthesia.RésuméObjectifL’anesthésie épidurale peut être difficile à réaliser pendant la grossesse. Nous avons voulu évaluer les possibilités d’apprentissage de l’échographie comme approche diagnostique de la région épidurale.MéthodeDeux groupes de résidents ont réalisé leurs 60 premières anesthésies épidurales sous supervision. Un premier groupe a procédé de manière traditionnelle selon la technique de perte de résistance (groupe témoin = GT). Lautre groupe a fait la même chose, mais bénéficiait de l’assistance de l’échographie qui donnait des informations sur les meilleurs site, profondeur et angle de ponction (groupe d’échographie = GE). La réussite était une anesthésie épidurale adéquate exigeant au plus trois essais, affichant un score de moins de I à l’échelle visuelle analogique et n’exigeant pas de modifier la technique anesthésique, ni de faire la ponction à un autre niveau vertébral. De plus, l’intervention d’un superviseur constituait un échec.RésultatsUn taux de un succès de 60% ± 16% a été noté dans le GT après les 10 premières tentatives suivies par une hausse presque continue de la courbe d’apprentissage. Pendant les 50 anesthésies suivantes, le taux est monté à 84 %. Dans le GE, le taux a été d’abord de 86 % ± 15 %, puis, pour les 50 anesthésies suivantes, il s’est élevé à 94 %. La différence intergroupe demeurait donc significative. (P < 0,001).ConclusionLutilisation de l’échographie dans l’enseignement de l’anesthésie épidurale obstétricale, comparée à la méthode traditionnelle d’enseignement, a montré un taux de succès plus élevé pendant les 60 premiers essais. Cette expérience démontre la valeur de l’échographie dans l’enseignement et l’apprentissage de l’anesthésie obstétricale régionale.

ADDITION OF CLONIDINE ENHANCES POSTOPERATIVE ANALGESIA FROM EPIDURAL MORPHINE : A DOUBLE-BLIND STUDY

This study was undertaken to evaluate the analgesic effect of the combination of epidural morphine and clonidine versus epidural morphine alone in patients with postoperative pain. A randomized double-blind design was used, and 91 patients scheduled for post-operative pain relief by epidural morphine were studied. Patients received either a continuous epidural infusion of morphine and clonidine (group 1; n = 45) or morphine alone (group 2; n = 46) over the 72 h after major abdominal surgery. In the first 24 h, the dose of morphine was 6 mg per 24 h; during the second 24 h, it was decreased to 4 mg per 24 h; and in the final 24 h, it was decreased to 2 mg per 24 h in both groups. Group 1 patients received clonidine (450 micrograms) during each 24-h period. Additional epidural bolus injections of 2 mg morphine and intravenous meperidine were given on demand. The pain score, blood pressure, heart rate, respiratory rate, and relative forced vital capacity were measured at fixed times during the first 72 h after operation. Total consumption of analgesics and side effects were recorded. Although the total consumption of analgesics was significantly higher in group 2 (P less than 0.05), pain scores were lower in group 1 than group 2 during the entire observation period (P less than 0.05). Epidural clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. Due to the better pain relief in group 1, the forced vital capacity was increased (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Paramedian access to the epidural space: the optimum window for ultrasound imaging

STUDY OBJECTIVE To establish a useful ultrasonic approach to the epidural space so as to optimize pre-puncture diagnostics. DESIGN Prospective study. SETTING University clinic. PATIENTS 60 participants (19 to 34 years of age), 40 healthy volunteers (20 male, 20 female) and 20 parturients. INTERVENTIONS Ultrasound scanning of the lumbar spine was performed at the L(3)-L(4) vertebral interspace. Three ultrasound planes were employed: the transverse, median, and paramedian longitudinal approaches. MEASUREMENTS We compared the width of the ultrasound-permeable area in the median and paramedian planes and assessed the visibility of the epidural space and its surrounding structures. MAIN RESULTS In the paramedian plane, the permeable window was larger (p < 0.001) than in the median approach. The visibility of the ligamentum flavum (p < 0.0001), dura mater (p < 0.0001), and cauda equina (p < 0.0001) was significantly higher. Pulsation of epidural vessels could be observed more frequently (p < 0.0001) in the paramedian plane. CONCLUSIONS The longitudinal paramedian plane provided information about the epidural space depth in excellent imaging quality. The additional information might be beneficial in epidural anesthesia and in other clinical specialties (e.g., neurosurgery, trauma care).

Inhaled Nitric Oxide Inhibits Human Platelet Aggregation, P-Selectin Expression, and Fibrinogen Binding In Vitro and In Vivo

BACKGROUND Recent data suggest that inhaled NO can inhibit platelet aggregation. This study investigates whether inhaled NO affects the expression level and avidity of platelet membrane receptors that mediate platelet adhesion and aggregation. METHODS AND RESULTS In 30 healthy volunteers, platelet-rich plasma was incubated with an air/5% CO2 mixture containing 0, 100, 450, and 884 ppm inhaled NO. ADP- and collagen-induced platelet aggregation, the membrane expression of P-selectin, and the binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa receptor were determined before (t0) and during the 240 minutes of incubation. In addition, eight patients suffering from severe adult respiratory distress syndrome (ARDS) were investigated before and 120 minutes after the beginning of administration of 10 ppm inhaled NO. In vitro, NO led to a dose-dependent inhibition of both ADP-induced (3+/-3% at 884 ppm versus 70+/-6% at 0 ppm after 240 minutes; P<.001) and collagen-induced (13+/-5% versus 62+/-5%; P<.01) platelet aggregation. Furthermore, P-selectin expression (36+/-7% of t0 value; P<.01) and fibrinogen binding (33+/-11%; P<.01) were inhibited. In patients with ARDS, after two who did not respond to NO inhalation with an improvement in oxygenation had been excluded, an increase in plasma cGMP, prolongation of in vitro bleeding time, and inhibition of platelet aggregation and P-selectin expression were observed, and fibrinogen binding was also inhibited (19+/-7% versus 30+/-8%; P<.05). CONCLUSIONS NO-dependent inhibition of platelet aggregation may be caused by a decrease in fibrinogen binding to the platelet GP IIb/IIIa receptor.

Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial

Background and objective Sugammadex, a modified γ-cyclodextrin, is a selective relaxant-binding agent designed to reverse the effects of the steroidal neuromuscular blocking agents rocuronium or vecuronium. This study compared the efficacy of sugammadex and neostigmine for reversal of neuromuscular blockade induced by rocuronium for facilitating elective surgery. Methods This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia. Neuromuscular blockade was monitored using acceleromyography and a train-of-four (TOF) mode of stimulation. Patients were randomly allocated to receive sugammadex 2.0 mg kg−1 or neostigmine 50 μg kg−1 (with glycopyrrolate 10 μg kg−1) at reappearance of the second response of the TOF (mean 16% twitch height of first response) after the last dose of rocuronium. Safety was evaluated by assessing adverse events, laboratory variables and vital signs. Results Time to recovery of the TOF ratio of 0.9 after sugammadex compared with neostigmine was significantly shorter (P < 0.0001), being 1.5 versus 18.6 min (geometric means). Predictability of response was greater with sugammadex than neostigmine: with 98% of sugammadex patients versus 11% of neostigmine patients recovering to a TOF ratio of 0.9 within 5 min. There were no clinical events related to residual neuromuscular blockade or reoccurrence of blockade. Serious adverse events were observed in two sugammadex-treated patients and in three neostigmine-treated patients, respectively, but none were considered related to study drugs. Conclusion Sugammadex achieved significantly faster recovery of neuromuscular function after rocuronium to a TOF ratio of 0.9 compared with neostigmine (Clinicaltrials.gov identifier: NCT00451217).

Use of perflubron emulsion to decrease allogeneic blood transfusion in high-blood-loss non-cardiac surgery: results of a European phase 3 study.

Background This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care. Methods Subjects (N = 492) with hemoglobin concentrations of 12–15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 ± 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 ± 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 ± 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 ± 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 ± 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion. Results Both groups had similar hemoglobin concentrations at screening (13.5 ± 1.0 g/dl) and at discharge: 10.8 ± 1.2 g/dl (PFC) and 11.1 ± 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53%vs. 43%, P < 0.05), and fewer erythrocytes were transfused (1.5 ± 4.8 vs. 2.1 ± 3.9 units; median, 0 vs. 1 unit;P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss ≥ 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26%vs. 16% in the PFC and control groups, respectively;P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 ± 2.9 vs. 4.9 ± 2.4 units; median 2 vs. 4 units;P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%;P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4%vs. controls, 2%) was not statistically significant. Conclusions Augmented acute normovolemic hemodilution with PFC reduces transfusion needs in patients undergoing noncardiac surgical procedures with blood loss 20 ml/kg or greater.