BACKGROUND:The 2% formulation of the intravenous anaesthetic agent, propofol (Diprivan), delivers half the amount of lipid compared with the original 1% formulation. This may provide an acceptable alternative for patients who have an impaired ability to metabolise lipids.METHODS:This study was a multicentre, randomised, open comparison of parallel groups. Seventy-three adult patients undergoing elective craniotomy in neurosurgery were randomised to receive either propofol 1% (10 mg/ml) or propofol 2% (20 mg/ml) for induction and maintenance of anaesthesia.RESULTS:Analysis of induction time (199 s, 1%; 202 s, 2%; p > 0.05) and induction dose (1.13 mg/kg, 1.12 mg/kg; p > 0.05) shows that propofol 1% and propofol 2% are pharmacodynamically equivalent. Both formulations were similar regarding overall administration rates, recovery times, haemodynamic variables and tolerability. Plasma triglyceride levels, were lower in the propofol 2% group compared with the propofol 1% group, and significantly lower (p < 0.05) from 1 to 4 hours after induction.CONCLUSIONS:We conclude that propofol 2% is as effective and as well-tolerated as propofol 1% for anaesthesia and is an acceptable alternative to propofol 1% in patients undergoing elective craniotomy in neurosurgery. The lower lipid load suggests it may be of particular benefit to patients with disorders of lipid metabolism.

BACKGROUND Evaluation of outcome after CPR in severe hypothermic patients. DESIGN Perspective study from October 1995 to April 1996. SETTING First aid team of Italian Red Cross, Busto Arsizio (Varese), Italy. METHODS A population of 22 patients in cardiac arrest in which CPR was performed immediately after rescue team's arrival is studied. ECG, core temperature, SpO2 and MAP were monitored whereas vital parameters were present during Basic Life Support. Outcome after CPR was evaluated with GOS scale. RESULTS It has been observed that severe hypothermia and time of cardiac arrest impact on the clinical outcome after CPR. The high mortality rate after CPR with BLS standard is worsened by a core temperature < or = 33 degrees C. CONCLUSIONS Severe hypothermia seems to have a dangerous effect upon outcome after cardiopulmonary resuscitation; heating systems for body temperature could prevent this situation improving CPR results.

BACKGROUND Evaluation of outcome after CPR in severe hypothermic patients. DESIGN Perspective study from October 1995 to April 1996. SETTING First aid team of Italian Red Cross, Busto Arsizio (Varese), Italy. METHODS A population of 22 patients in cardiac arrest in which CPR was performed immediately after rescue team's arrival is studied. ECG, core temperature, SpO2 and MAP were monitored whereas vital parameters were present during Basic Life Support. Outcome after CPR was evaluated with GOS scale. RESULTS It has been observed that severe hypothermia and time of cardiac arrest impact on the clinical outcome after CPR. The high mortality rate after CPR with BLS standard is worsened by a core temperature < or = 33 degrees C. CONCLUSIONS Severe hypothermia seems to have a dangerous effect upon outcome after cardiopulmonary resuscitation; heating systems for body temperature could prevent this situation improving CPR results.

BACKGROUND:Evaluation of outcome after CPR in severe hypothermic patients. DESIGN:Perspective study from October 1995 to April 1996. SETTING:First aid team of Italian Red Cross, Busto Arsizio (Varese), Italy. METHODS:A population of 22 patients in cardiac arrest in which CPR was performed immediately after rescue team's arrival is studied. ECG, core temperature, SpO2 and MAP were monitored whereas vital parameters were present during Basic Life Support. Outcome after CPR was evaluated with GOS scale. RESULTS:It has been observed that severe hypothermia and time of cardiac arrest impact on the clinical outcome after CPR. The high mortality rate after CPR with BLS standard is worsened by a core temperature < or = 33 degrees C. CONCLUSIONS:Severe hypothermia seems to have a dangerous effect upon outcome after cardiopulmonary resuscitation; heating systems for body temperature could prevent this situation improving CPR results.

BACKGROUND:In a prior study the 21-aminosteroid (lazaroid) U74389F provided in vivo protection from oxidative stress when used as a preventive therapy in ischemia-reperfusion injury in the kidney. As the cell membrane is the principal site for lipoperoxidation, in the current study the very lipophilic 2-methylaminochroman U83836E, a recently developed lazaroid, was administered to rats at 3 mg/kg before renal ischemia-reperfusion. In addition to the biochemical parameters, the renal function and the histological appearance were carefully evaluated.METHODS:Glutathione, adenine nucleotides and lipid peroxidation products were determined in kidneys reperfused for 2 and 24 hours after 90 minutes of ischemia. Renal function was assessed by plasma creatinine, and renal injury by histological examination.RESULTS:Reperfusion-induced glutathione oxidation, expressed as an oxidized-to-total glutathione ratio, was significantly attenuated both after 2 and 24 hours of reperfusion by treatment with U83836E. Adenosine triphosphate (ATP) was still significantly depleted after 24 hours in the control group, while at the same time treated animals had already recovered to baseline values. Lipid peroxidation products were significantly lower in lazaroid-groups both after 2 and 24 hours of reperfusion. Renal function after 24 hours of reperfusion was notably better in the treated rats. Histological examination confirmed the protective action of the drug. After 24 hours the control group showed large areas of parenchymal hemorrhage and necrosis with dilated tubules and blood vessel thrombosis, while treated animals showed small necrotic areas with a background of mild interstitial inflammatory cells.CONCLUSIONS:Our results suggest that there is a protective effect of U83836E in ischemia-reperfusion injury, in that tissue damage due to oxidative stress is reduced, thus ameliorating renal function impairment.

We examined the effects of the administration of 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1,4,9( 11)-triene-3,20-dione, monomethansulfonate (U74389F), a 21-aminosteroid and so-called lazaroid, that is characterized by an inhibitory activity against iron-dependent lipid peroxidation, on ischemia-reperfusion renal injury in a rat model. After either 60 or 90 min of ischemia, plus 2 or 24 h of reperfusion, kidneys were assayed for glutathione, adenine nucleotides and lipid peroxidation products. 60 min of ischemia produced too little oxidative stress and/or too much spontaneous recovery to allow visualization of the protective effect of the drug. 90 min of ischemia followed by reperfusion induced significant glutathione oxidation, the free oxidized glutathione to total glutathione redox ratio (%) being enhanced from 4.6 +/- 0.7% before kidney clamping to 11 +/- 1 and 8.6 +/- 1.4% at 2 and 24 h reperfusion, respectively. Treatment with the lazaroid provided significant protection against this oxidation (4.9 +/- 1.05% at 24 h reperfusion). Results of lipid peroxidation confirmed the antioxidant effect of the lazaroid. In conclusion this study provides evidence for a protective role of the tested lazaroid against ischemia-reperfusion renal injury in the rat.

OBJECTIVE:To verify the applicability and the clinical significance of left ventricular wall stress determinations by intraoperative transesophageal echocardiography (TEE) during resections of abdominal aortic aneurysms.DESIGNS:Prospective comparison of changes in left ventricular wall stress between two groups of patients with and without coronary artery disease.SETTING:Operatory room of Universitary Institute.PATIENTS:Twenty-three patients with abdominal aortic aneurysms; 8 had clinically evident coronary artery disease (CAD+); 15 patients did not have clinical or electrocardiographic evidence of coronary artery disease (CAD-).INTERVENTIONS:Resection of the aortic aneurysm and insertion of a synthetic prosthesis.MEASUREMENTS AND MAIN RESULTS:During operation transesophageal monitoring of left ventricular volumes and wall stress was performed during induction of anesthesia (T1), for two minutes after aortic clamping (T2), at the end of the proximal anastomosis (T3), for two minutes after aortic declamping (T4) and at the end of the procedure (T5). Circumpherential stress at end systole (sES) and end diastole (sED) was more sensitive than hemodynamic and volumetric parameters in detecting changes i function of the ischemic myocardium. In detail we observed: a significant increase of sES in CAD+versus CAD- at T2: 98 (sd 18) vs 83 (sd 14) 10(3) dyne/cm2. a significant increase of sED in CAD + versus CAD- at T2: 28.5 (sd 6) vs 22 (sd 4.5) 10(3) dyne/cm3. a similar trend of sES and sED at T4: 73 (sd 20.5) vs 46 (sd 15) 10(3) dyne/cm2 and 31 (sd 12) vs 16 (sd 7.7) 10(3) dyne/cm2 respectively. a significant increase of sED in CAD + at T5 (about 20' after T4): 26.5 (sd 9.5) vs 16 (sd 5.2) 10(3) dyne/cm2 which is expression of a persistent reduction of ventricular compliance in the ischemic patients.CONCLUSIONS:Wall stress modifies MVO2 and subsequently is sensitive in detecting changes in myocardial performance. TEE could valuably integrate routine hemodynamic monitoring of patients with coronary heart disease who undergo surgical resection of abdominal aortic aneurysms.

Antiadrenergic Interventions and Prevention of Sudden Death after MI. Introduction: Growing evidence points to sympathetic hyperactivity as one critical trigger for life‐threatening arrhythmias among postmyocardial infarction patients. Methods and Results: We have evaluated, in a placebo‐controlled multicenter study, the efficacy of a β‐adrenergic blocking agent (oxprenolol 160 mg) and of a selective left cardiac sympathetic denervation in preventing sudden death in patients with a first and anterior myocardial infarction. Two patient groups were studied. The high‐risk group included 144 patients who survived a myocardial infarction complicated by either ventricular tachycardia or fibrillation. The relatively low‐risk group included 869 patients whose myocardial infarction did not have these complications; they were allocated only to placebo or oxprenolol. Randomization took place 30 days postmyocardial infarction; mean follow‐up was 22 months. In the high‐risk group the sudden cardiac death (crude rate) in the placebo subgroup was indeed high (21.3%), and was strikingly reduced to 2.7% and to 3.6% by oxprenolol and by left cardiac sympathetic denervation, respectively (P < 0.05). In the low‐risk group the sudden cardiac death (crude rate) in the placebo subgroup was 5.2% and was still reduced by oxprenolol to 1.6% (P < 0.05). The results for total mortality were quite similar to those for sudden death iu both groups. Conclusion: This study, unique for the populations studied and for one of the treatments used, demonstrates that pharmacologic and surgical antiadrenergic interventions significantly reduce sudden cardiac death in postmyocardial infarction patients at high and at low risk. With due consideration to the relatively small size of the high‐risk group, it seems reasonable to suggest that left cardiac sympathetic denervation may be considered as a possible alternative for high‐risk patients with contraindications to beta blockers. (J Cardiovasc Electrophysiol, Vol 3, pp. 2–16, February 1992)

BACKGROUND:Long QT syndrome (LQTS) is a congenital disorder accompanied by a high incidence of sudden cardiac death. beta-Adrenergic blockade is the therapy of choice, and it is successful in 75-80% of patients. For those in whom cardiac events (syncope or cardiac arrest) are not prevented by beta-blockade, experimental studies suggest that left cardiac sympathetic denervation (LCSD) may be useful.METHODS AND RESULTS:We identified 85 LQTS patients worldwide who underwent LCSD, and we provide here the first large-scale evaluation of its efficacy. The time interval between the first cardiac event and LCSD and the follow-up period after LCSD were similar (5.6 +/- 6.1 versus 5.9 +/- 5.7 years). The mean age of the patients at surgery was 20 +/- 13 years. LCSD was followed by highly significant (p less than 0.0001) decreases in the number of patients with cardiac events (from 99% to 45%), in the number of cardiac events per patient (from 22 +/- 32 to 1 +/- 3), and in the number of patients with five or more cardiac events (from 71% to 10%). There were seven sudden deaths (8%), and the 5-year survival rate was 94%. The marked reduction in the incidence of tachyarrhythmic syncope suggests that LCSD has also reduced the risk for sudden death in this high-risk population.CONCLUSIONS:The present findings demonstrate that for LQTS patients who continue with syncope or cardiac arrest despite the use of beta-blockers, LCSD is a very effective therapy.

24 of 184 patients with vertebro-medullary trauma admitted to the Neurosurgery Clinic of Milan University in the years 1976-1988 have been examined. A common feature of these was a myelic lesion (transverse, complete or incomplete) at cervical level in which respiratory problems had made a period of intensive care indispensable. The purpose of the research was to assess the reliability of certain parameters in establishing patient prognosis. The following parameters were compared: clinical, objective and instrumental examination for a strictly neurological evaluation and for an evaluation of general condition, quantification of the same clinical examination through two scales, the Sunnybrook Cord Injury Scale (SCIS) for the neurological factor and the APACHE II for general condition, the type of treatment, with the same basic medical-resuscitation treatment. The result of the surgery or non-surgery was considered a posteriori. It is concluded that, in the case of the patients considered (high myelic lesion) the prognosis must be split into two different moments that the patient goes through in succession: the acute phase and the stabilisation phase. In the first phase, in which the vital functions are involved, the SCIS and APACHE II scales (with their sum) have great prognostic value; in the second phase, certain values, already considered on the APACHE II scale, are comparable in all patients and the prognostic problem is based on the other scale (SCIS) and on the adjuvant neurophysiological techniques. The very distinction between the two different phases that the patient traverses appears important also for the purposes of surgical indication.2

A consecutive series of 41 patients aged less than 16 and admitted to the Department of Neurosurgery of the University of Milan in the period 1977-1978 following serious cranioencephalic trauma with Glasgow Coma Score (GCS) less than or equal to 7, duration of coma longer than 24 h and CT picture of diffuse lesion has been examined. These patients account for 5% of the paediatric cranial traumas observed in the same period and 66% of those in a state of coma. The CT picture made it possible to split patients into 3 groups: a) those without visible cerebral lesions and with subarachnoid and cisternal spaces present; b) those with small hyperdense lesions due to intraparenchymal or median/paramedian subcortical shearing lesions; c) those with marked constriction or absence of the 3rd ventricle and of the perimesencephalic cisterns. The first two pictures (a, b) were considered to be the expression of diffuse axonal damage, the last (c) of diffuse cerebral swelling. Intracranial pressure was monitored in about 50% of patients. The overall outcome of the series was favourable in more than 68% of cases with total mortality of 26.8%. Analysis of individual tomographic categories, however, showed that whereas the group of patients with diffuse axonal lesion presented nil mortality, those with diffuse cerebral swelling had 52% mortality owing to the onset of refractory intracranial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of propofol on cerebral blood flow velocity, cerebrospinal fluid pressure, cerebral perfusion pressure and mean arterial pressure were studied during induction in 25 patients scheduled for elective craniotomy. Premedication consisted of only atropine sulphate 0.007 mg/kg (im) 45 min before induction. Measurements were made or derived at time zero and 1, 2, 3, 4 and 5 min after an induction dose of propofol (2.5 mg/kg). Patients were retrospectively stratified into two groups, according to cerebrospinal pressure basal values: (i) lower than 10 mmHg (10 pts) and (ii) higher than 10 mmHg (15 pts). Cerebral blood flow velocity, measured by transcranial Doppler, fell in all the patients, but the reduction was significant at 1,2, 3 and 4 min only in the group with high CSFpressure, while it never reached the critical value of 10 cm/s. Cerebrospinal fluid pressure and mean arterial pressure decreased in both groups of patients and the fall reached a statistical significance at 1 and 2 min in the group with higher baseline CSF pressure, only at 1 min: a parallel decrease of CPP was recorded, but it was not significant. Thus propofol decreases CSF pressure without hazardous effects on cerebral blood velocity and on cerebral perfusion pressure and seems to be a suitable anaesthetic agent in controlling high cerebrospinal fluid pressure in neuroanaesthesia.