Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer.

BACKGROUND: Because of the increasing number of long-term survivors of metastatic testicular germ-cell cancer, a general concern has been secondary morbidities, especially cardiovascular risk factors. PATIENTS AND METHODS: Thirty-two patients treated with cisplatin- and doxorubicin-containing chemotherapy > or = 13 years before the time of analyses were evaluated for neuro-, oto-, pulmonary-, vascular- and gonadal toxicity including evaluation of myocardial damage and cardiovascular risk factors and analysis of microcirculation. RESULTS: Thirty percent of the patients showed abnormal left ventricle function. Elevated follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in 75% of patients were often associated with low testosterone levels. Elevated total cholesterol levels were found in 82% and higher triglyceride levels in 44% of patients, most of them were overweight. About 25% of the patients developed diastolic arterial hypertension after chemotherapy. Reduced hearing was confirmed in 23% of patients, especially at frequencies higher than 3000 Hz. Moreover, 53% of patients presented transient evoked otoacoustic emissions. In 38% of patients non-symptomatic neuropathy was detected, in 28% symptomatic neuropathy, and in 6% disabling polyneuropathy. In 80% of patients with neuropathic symptoms additional morphological and functional abnormalities were found by nailfold capillary videomicroscopy, compared to only 57% of the patients without neuropathic symptoms. CONCLUSIONS: Patients cured by cisplatin-based chemotherapy for metastatic testicular cancer have to be cognizant of their unfavorable cardiovascular risk profile, that might be a greater risk than developing a relapse or second malignancy.

The depolarization near-field scanning optical microscope: comparison of experiment and theory.

The depolarization near-field scanning optical microscope allows for sub-wavelength optical resolution with uncoated optical fibre tips. We show by a simple thought experiment, by numerical solution of the Maxwell equations for a realistic geometry, and by direct experiments, that this novel apparatus images gradients of the dielectric function of a sample in the direction of the incident electric field vector. The near-field images obtained from experiment and theory agree well.

Comparison of time course of neuromuscular blockade in young children following rocuronium and atracurium.

In order to compare the neuromuscular effects following rocuronium 0.6 mg kg-1 and atracurium 0.5 mg kg-1 30 children aged from 18 to 67 months were studied under the same anaesthetic conditions. After induction of anaesthesia with etomidate and fentanyl, neuromuscular blockade was monitored by recording the electromyographic response of the adductor pollicis muscle to a supramaximal train-of-four (TOF) stimulation of the ulnar nerve at 2 Hz for 2 s at 20-s intervals. Intubation was performed when more than 90% muscle relaxation was achieved, thereafter anaesthesia was maintained with 70% nitrous oxide in oxygen and isoflurane 0.5% end-tidal. Mean onset of action was significantly faster following rocuronium (86 +/- 44.9 s) (mean +/- SD) compared with atracurium (126.3 +/- 61.0 s). Clinical duration with rocuronium was 22.8 +/- 5.31 min and thus significantly shorter than that of atracurium, which was 31.5 +/- 6.01 min. A statistically significant difference between rocuronium and atracurium also had been found for recovery of T1 to 50%, 75% and 90% as well as for the time taken to a TOF ratio of 70%. The recovery index for rocuronium and atracurium was not significantly different with 9.2 +/- 3.43 min and 10.9 +/- 2.65 min, respectively. Thus, rocuronium may be more advantageous than atracurium for short-lasting surgical procedures in young children.

Alveolo-capillary protein permeability and lung function in patients with late pulmonary complications after allogeneic bone marrow transplantation.

A prospective study was performed to identify markers predictive for the development of pulmonary complications in the early (<50 days) and late (>50 days) phase after bone marrow transplantation (BMT). The characterization of BMT patients with early or late pulmonary complications revealed clear-cut differences. Early and long term increase of alveolo-capillary protein permeability was associated with smoking and was found in 20 patients developing pulmonary complications within 50 days after BMT (group 1). The 22 patients who developed such complications thereafter (group 2) had more acute graft vs host disease than 66 patients who remained free of these complications for a minimum of 1 year. Concentrations of bronchoalveolar lavage (BAL) fluid albumin (alb) and serum beta2-microglobulin (S-beta2m) were determined 10 days before BMT, on days 1, 30, and 40 after BMT, whereas lung function tests were performed before BMT, after discharge from the hospital, and 6 months as well 1 year after BMT. Using cut-off values for BAL fluid alb (>2.3 mg/dl) and S-beta2m (>0.8 mg/liter) we could significantly discriminate 12 patients out of 19 group 1 patients (early pulmonary complications) as well as 9 out of 21 group 2 patients (late pulmonary complications) from 12 out of 64 group 3 patients (without such complications) 1 day after BMT. Our results demonstrate that early increased alveolo-capillary protein permeability defines a patient population at risk to develop pulmonary complications later than 50 days after BMT with up to 1 year significantly decreased lung volumes (FEV1, 73% predicted, VC, 85% predicted).

Intubating conditions and onset of action after rocuronium, vecuronium, and atracurium in young children.

To evaluate muscle relaxant onset times and tracheal intubating conditions, 60 children (ASA physical status I or II) aged 18 to 72 mo were randomly assigned to receive a bolus of either rocuronium 0.6 mg/kg, vecuronium 0.1 mg/kg, or atracurium 0.5 mg/kg. After induction of anesthesia with etomidate 0.2-0.4 mg/kg and fentanyl 1-3 mg/kg, lungs were ventilated with 50% nitrous oxide in oxygen via a face mask. The evoked electromyogram of the adductor pollicis to a train-of-four stimulation every 20 s was monitored. After administration of the muscle relaxant, endotracheal intubation was attempted every 30 s, beginning 30 s after drug administration, until intubation could be achieved with good or excellent conditions. Rocuronium produced acceptable intubating conditions significantly faster (all tracheas intubated within 60 s) compared with vecuronium (120 s) and atracurium (180 s). The quality of intubating conditions at the time of completed intubation was rated significantly better with rocuronium than with vecuronium or atracurium. However, onset to 95% block at the adductor pollicis muscle was not significantly different after rocuronium (92 +/- 46.9 s), vecuronium (112 +/- 33.3 s), or atracurium (134 +/- 57.1 s), and mean neuromuscular block achieved at the point of successful intubation was not complete in all groups. We conclude that clinically acceptable intubating conditions are produced more rapidly with rocuronium than with atracurium or vecuronium.

Deep sedation with propofol in preschool children undergoing radiation therapy.

Immobilization of children undergoing radiation therapy always requires anaesthesia. Deep sedation with continuous infusion of propofol and spontaneous breathing, (we call it ¿sedative anaesthesia'), may be an alternative to general anaesthesia with intubation and controlled ventilation. This clinical report deals with 155 anaesthetics performed in 11 consecutive paediatric oncology patients, mean age 30 months (range 19-42), who required radiation therapy for from seven to 33 consecutive days. Mean duration of anaesthesia was 18 ( +/- 11) mins. For induction, a loading dose of 3.6 (SD +/- 0.59) mg.kg-1 propofol was administered immediately followed by a continuous infusion of 7.4 ( +/- 2.2) mg.kg-1.h-1 for maintenance of anaesthesia. There were no complications of clinical importance involving respiration, circulation or neurology, except for one short episode of transient desaturation, which was managed by suctioning and changing head position. Children opened their eyes spontaneously four ( +/- 3.7) min after discontinuing the propofol infusion and could be discharged about 30 mins later. Tachyphylaxis or unpleasant side effects during and after anesthesia have not been observed. Sedative anaesthesia with propofol seems to be an excellent method to immobilize paediatric patients during radiotherapeutic procedures.

[Plethysmechanomyography (PMG). A simple method for monitoring muscle relaxation]. / Die Plethysmo-Mechanomyographie (PMG). Eine einfache Methode zur Erfassung der Muskelrelaxation.

Ideal evaluation of neuromuscular blockade can be done by mechanical or electromyographical registration of muscle contractions evoked by ulnar nerve stimulation. Unfortunately, devices needed for such registration are expensive or complicated to set up, and thus are not often used for routine monitoring in anaesthesia. In this study, we describe a simple and low-priced method permitting intra- and postoperative monitoring of neuromuscular blocking agents. The accuracy of plethysmomechanomyography (PMG) was evaluated by comparing simultaneous electromyographic (EMG) and plethysmographic measurements. METHODS. For plethysmographic registration of muscle response to nerve stimulation a simple infusion system is twisted there to five times around one hand and connected to an anaesthetic monitor via a pressure transducer. The drip chamber is fixed about 20 cm above the hand (Fig. 1). Then, the infusion system is then filled up-with physiologic saline solution and the clamp is nearly closed. Electric stimulation can be carried out using any nerve stimulator. Using this method, PMG mainly records the contractions of abductor digiti minimi muscle, but also partly those of the interossei. Evoked muscle contractions cause stretching of the infusion system, which leads to pressure changes proportional to the strength of contraction. The muscle response to "train-of-four" (TOF) stimulation of the ulnar nerve was recorded simultaneously by EMG and PMG in 11 patients (ASA class I or II) undergoing neurosurgical procedures and therefore requiring muscle relaxation. After induction of anaesthesia by injection of etomidate and fentanyl, supramaximal stimulation and control values (T0) were defined. Anaesthesia was maintained by supplementation with nitrous oxide/oxygen (1:2) and muscle relaxation was carried out with vecuronium. We used the integrated nerve stimulator of a Datex Relaxograph NMT-100 EMG monitor and proceeded to stimulate the ulnar nerve at the forearm with supramaximal strength. The PMG was registered by a Siemens Siredoc 220 printer connected to a Siemens Sirecust 1281 anaesthetic monitor. First twitch ratio (T1/T0) and TOF ratio (T4/T1) were calculated from these recordings. The EMG recordings were made by a Datex Relaxograph NMT-100 monitor, which automatically computes T1/T0 and T4/T1. The comparison of EMG and PMG values was carried out by simple linear regression. Statistical evaluation was performed using analysis of variance. RESULTS. A plethysmographically registered graph of the TOF-evoked muscle response is illustrated in Fig. 2. Simultaneous EMG and PMG recordings of onset and recovery from a nondepolarizing blockade are shown in Fig. 3. A strong positive correlation (P < 0.001) of EMG and PMG was found with correlation coefficients of 0.98 for T1/T0 and of 0.97 for T4/T1. The mean difference between values of both methods was 5%, maximally 18% (T1/T0) and 20% (T4/T1). CONCLUSIONS. Mechanomyography and EMG are well established methods of neuromuscular monitoring. Our data demonstrate that PMG provides a reliable measurement of neuromuscular transmission that correlates well with EMG. Since only materials of daily use in anaesthesia are needed, no substantial costs will arise when the plethysmographic method of measurement is used for routine anesthetic monitoring.

[The effect of different types of anesthetic respirators on oxygenation and ventilation in infants during short-term anesthesia. A study using transcutaneous PO2 and PCO2 monitoring]. / Der Einfluss verschiedener Narkosebeatmungsverfahren auf Oxygenierung und Ventilation von Säuglingen. Eine Untersuchung mittels transkutaner PO2- und PCO2-Messung.

Monitoring of ventilation in infants is difficult and often not very reliable. In this study, transcutaneous measurement of blood gas tensions was used to investigate the influence of four different modes of ventilation on oxygenation and ventilation in anaesthetized infants. METHODS. In a randomised study, transcutaneously measured PO2 (tc-PO2) and PCO2 (tcPCO2) tensions were continuously registered in 42 ASA class I and II infants between 3 and 24 weeks of age undergoing minor surgical procedures (inguinal hernia repair). Two breathing systems combined with different modes of ventilation were evaluated: manual ventilation with Kuhn's T-piece system and face mask (group A; n = 11) or endotracheal tube (group B; n = 10); manual ventilation with paediatric circuit system and face mask (group C; n = 11); and mechanical ventilation with paediatric circle system, endotracheal tube, and positive end-expiratory pressure (PEEP) 3 cm H2O (group D; n = 10). Transcutaneous values were measured by a combined tcPO2/PCO2 electrode (E 5277, Radiometer). Anaesthesia was maintained by controlled ventilation with N2O/O2 (67%/33%) and halothane 0.5-1.5 vol.%. Surgical and anaesthetic techniques were standardized and the anaesthetist was blinded to the measured values. RESULTS. Preoperative mean tcPO2 values while spontaneously breathing air ranged between 69 and 75 mmHg in all patients. During anaesthesia and controlled ventilation (FiO2 = 0.33), there was a significant increase in tcPO2 (P < 0.01) in 3 groups: in groups A and D mean tcPO2 increased to 90-100 mmHg and in group C to 110-120 mmHg. In contrast, tcPO2 in group B reached only 75-80 mmHg, which was not considered significant. Postoperatively, tcPO2 immediately reached baseline values in all patients (Fig. 2). Compared to preoperative values, the alveolar-tcPO2 difference (AtcDO2) significantly increased during anaesthesia in all groups (Fig. 3). The tcPCO2 measurements revealed marked alveolar dysventilation, with hyperventilation supervening in groups A, B, and D; in group C, however, most (7 of 11) infants were normoventilated (Fig. 4). CONCLUSIONS. Adverse effects of anaesthesia on pulmonary function in infants are caused by loss of the PEEP effect induced by the physiological subglottic stenosis. Endotracheal intubation and the increase in chest wall compliance during anaesthesia lead to a decrease in functional residual capacity (FRC) associated with premature airway closure and ventilation/perfusion mismatch. These pathophysiological disturbances result in a marked increase in AaDO2 and low arterial PO2 values despite high FiO2, as could be observed when intubated infants had been ventilated with a high-flow T-piece system (group B). Mechanical ventilation with a paediatric circuit system and endotracheal tube allows the use of low PEEP levels (group D), which may replace the lost subglottic function and partially restore the FRC. Ventilation by mask does not disturb the functional subglottic stenosis, and the impairment of pulmonary function will depend solely on the decrease in FRC caused by increased chest wall compliance (group A). If mask ventilation is combined with a paediatric circuit system (group C), the pressure relief valve produces a low PEEP of 2 to 3 cm H2O, which may partially counteract the decrease in FRC. With regard to oxygenation, the paediatric circle system proved to be superior to the high-flow T-piece system independent of whether children were ventilated via a face mask or an endotracheal tube. The group-specific differences in degree of dysventilation with manual ventilation show that the type of breathing system is important with regard to the size of the tidal volume delivered. Thus, tidal volumes will be unintentionally increased by the high fresh gas flow needed when a T-piece system is used. The lower flow and preadjusted pressure limit may prevent the delivery of excessive tidal volumes with the paediatric circuit system...

[Hemodynamics of coronary surgery patients following magnesium aspartate infusion]. / Hämodynamik koronarchirurgischer Patienten nach Magnesium-Aspartat-Infusion.

Hypertension is a common phenomenon in patients undergoing aortocoronary bypass grafting. This hypertension increases myocardial oxygen consumption and can be prevented by application of vasodilators. A possible cause is activation of the renin angiotensin system. Magnesium is a potent vasodilator and has a beneficial effect after myocardial ischaemia. The study was performed to analyse the influence of magnesium infusion on the haemodynamic status and plasma renin activity in patients undergoing aortocoronary bypass grafting. METHODS. Eighteen patients (NYHA classification II-III) undergoing bypass surgery were divided into two groups, a magnesium and a control group. The magnesium group (n = 9) received 0.8 mEq/kg per h magnesium aspartate as an infusion for 15 min while still awake. After induction of anaesthesia, the magnesium infusion was reduced to 0.2 mEq/kg per h and stopped after aortic cannulation was completed. Plasma magnesium levels and concentrations within erythrocytes were measured. Anaesthesia was induced by flunitrazepam (0.01 mg/kg), fentanyl (0.005 mg/kg) and pancuronium (0.1 mg/kg). After intubation, patients were normoventilated with N2O/O2 = 1:1 and isoflurane (0.5-1.0 vol%). Additional doses of fentanyl (0.0025 mg/kg) were injected before the incision and before sternotomy. Mean arterial pressure, heart rate, cardiac index, total peripheral resistance, pulmonary vascular resistance, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left ventricular stroke work index, right ventricular stroke work index, intrapulmonary shunt and plasma renin activity were evaluated at five predefined points: (1) prior to magnesium infusion; (2) after magnesium infusion; (3) 10 min following induction of anaesthesia under steady-state conditions; (4) after sternotomy; (5) after aortic cannulation. RESULTS. Concerning the haemodynamic parameters (MAP, RAP, PAP, PCWP) no significant difference between the two groups could be demonstrated. In the control group peripheral resistance (TPR) was higher following sternotomy and aortic cannulation than in the magnesium group. Magnesium prevented decrease of the cardiac index (CI) under steady-state conditions, during sternotomy and following aortic cannulation. Left and right ventricular stroke work indexes (LVSWI and RVSWI) were higher in the magnesium group. Plasma renin levels were not significantly different between the two groups. CONCLUSION. Patients undergoing cardiac surgery benefit from magnesium administration in the pre-bypass phase. Due to its vasodilating effect, magnesium lowers the output impedance of the left ventricle and improves cardiac pumping function. It opposes detrimental cardiovascular responses to sternotomy and following aortic cannulation. Also of importance is the advantageous effect of magnesium on cardiac arrest elicited by cardioplegia and for reactivation of the ischaemic myocardium.