Bench test assessment of the new Raumedic Neurovent-P ICP sensor: a technical report by the BrainIT group

Summary. Background. In clinical practice, fiberberoptic and piezo-electric ICP probes are often used for measuring intracranial pressure (ICP). A number of similar technologies, although performing well in bench test studies, have been shown to exhibit unacceptable zero drift, fragility or both during trials conducted under clinical conditions. Recently, a new technology has become available, the Neurovent-P (Raumedic AG+CO, Raumedic, Germany). As a pre-requisite for a clinical trial, we have conducted and report on bench test studies to confirm the manufacturers long term zero-drift performance for this technology.Method. In a test rig static tests (recording of 20mmHg pressure) and dynamic tests, ranging from 5 to 50mmHg have been performed.Findings. 10 ICP probes have been tested for a total of 60 days. All the catheters, after the connection with the ICU monitor displayed a static pressure of 0±1mmHg and did not required pre-insertion alteration. At five days, mean zero drift was 0.6±0.9mmHg. Overall, zero drift ranged from 0 to 2mmHg. At a fixed static pressure of 20mmHg, the mean recorded value was 20.6±0.8mmHg, ranging from 19 to 23mmHg. A regression analysis of the relationship between the applied pressure and the recorded pressure during the dynamic tests of the 10 catheters yielded a correlation coefficient R² of 0.997. Applying the Altman and Bland method to assess the bias and confidence limits for the Raumedic catheter responses during the dynamic tests against the applied gold-standard hydrostatic column pressures, the average bias of –0.66±0.85mmHg, with 95% CLs of –2mmHg and 1mmHg.Conclusions. Mean zero drift, after five days, was very small and long-term continuous recording of a stable pressure was very precise. The response at dynamic tests, i.e. the changes of pressure in a wide range, was excellent. The average bias of the Raumedic catheter compared with the hydrostatic column is very small. After this bench test, the next and most critical step will be to conduct a trial of this promising technology under more demanding clinical environment.     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

Detection of apoptotic gene expression in human osteoblast-like cells by cDNA microarrays

Global gene expression during the induction of ion pair-mediated apoptosis was evaluated by an apoptosis microarray system. Human bone marrow stromal cells were cultured in the presence of 10^–6M dexamethasone to promote osteogenesis. After 28 days, these cells expressed elevated alkaline phosphatase activity and maintained Cbfa1 expression even when challenged with an apoptogen. Apoptosis was initiated by treating cells with 3mM Ca²⁺ and 5mM Pi for 4h. ³²P-Labeled mRNA was hybridized to a human apoptosis microarray containing 205 cDNA fragments. We found that apoptosis influenced the expression of 15 genes mainly involved in cell cycle and cell signaling. These genes included IGFBPs and ERK1, known to play a role in cell survival; GST and GST mu, required for maintenance of thiol redox; TNFR1, a gene product that initiates cell death; and finally, BAD, a gene that encodes a proapoptotic protein. Real-time PCR analysis showed that the expression of ERK1, TNFR1, and GST was modulated by 1.89-, 2.66-, and 1.6 fold after 4h and by 1-, 1.91-, and 1.5 fold, respectively, after 8h treatment with the ion pair. In addition, we also measured the expression of Bcl-2 and Bax by quantitative RT-PCR. We noted that these two genes were increased 3.07 and 2.99 fold, respectively, after 8h treatment with the apoptogen. Results of this study suggest that the ion pair influenced ERK1 and TNFR1 signaling pathways and affected thiol metabolism, whereas Bcl-2 and Bax were expressed at late stages of the death process.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

Standardization of Ischemic Hepatic Failure in Pigs as a Model for Bioartificial Liver Assessment

Purpose. A standard protocol of ischemic liver failure in pigs was examined to establish a system for assessing the efficacy of a bioartificial liver, based on clinical practice. Methods. The portal blood flow was extracorporeally bypassed into the cervical jugular vein, using a centrifugal blood pump. The portal vein and hepatic artery were then ligated. Results. The maintenance protocol was established as follows: (1) the concentration of the inhaled anesthetic was decreased by 0.2% when the systolic blood pressure was 100mmHg; (2) the volume of an infusion containing 5% glucose was increased to 10ml/kg per hour when central venous pressure was 5mmHg; (3) 20ml of 50% glucose was injected intravenously when the blood glucose was 50mg/dl; (4) 2000 units of heparin was injected intravenously when the activated clotting time was 150s; (5) sodium bicarbonate was given when the blood pH was 7.3; (6) tidal volume was increased by 1ml/kg when the pCO₂ was 80mmHg; (7) oxygen was increased by 25% when the pO₂ was 100mmHg. No vasopressors were used in the experiment. Conclusion. Our protocol reduced the operating time and minimized the risk of data deviation that can arise from variations in operating techniques and individual animal conditions. This experimental model is also easy to use as a bridge to transplantation.     

31P and23Na nuclear magnetic resonance study on forebrain ischemia in rats with shift reagent Dy(TTHA)

³¹P and ²³Na nuclear magnetic resonance (NMR) spectroscopy was employed to study the dynamic changes in intracellular high-energy phosphates and sodium during 15min of forebrain ischemia and recirculation in in vivo rat brain. In the presence of the shift reagent Dysprosium triethylenetetramine-N,N,N,N,N,N-hexaacetic and [Dy(TTHA)], the sodium peak separated into two peaks, unshifted and shifted. During 15min of ischemia, the unshifted sodium peak decreased and the shifted sodium peak increased. With recirculation, the unshifted and the shifted sodium peaks returned to the preischemia level within 10min, but the shifted one increased during 30–60min. Intracellular high-energy phosphates and intracellular pH (pHi) decreased during 15min of ischemia and returned to the preischemia levels within 20min of recirculation. We conclude that the decrease in unshifted sodium peak during ischemia is due to the decrease in subarachnoid sodium and the cellular influx of interstitial sodium would be minimum. The increase in shifted sodium peak during ischemia is considered to be due to the dilatation of cerebral blood vessels and the increase in interstitial sodium which was transported from subarachnoid space.(Kurata M: ³¹P and ²³Na nuclear magnetic resonance study on forebrain ischemia in rats with shift reagent Dy(TTHA). J Anesth 7: 325–333, 1993)     

Hospital Readmissions Following Abdominal Aortic Aneurysm Repair

In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are well described. However, little is known about post-discharge readmission rates, lengths of stay, associated mortality, and costs. We examined 206 consecutive patients who underwent AAA repair at two American hospitals between 1998 and 2000. Index hospitalization and 6-month readmission data were extracted from a resource and cost accounting system used by both hospitals. Among the 206 patients, 183 survived until discharge (mortality rate 11.2%). Among the surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the readmissions occurred within two weeks of discharge, with patients presenting with a diverse array of complications. Nonelective repair and diabetes mellitus were independent predictors of hospital readmission (OR=2.83, 95% CI=1.25-6.40, p=0.01; OR=6.60, 95% CI=1.02-42.4, p=0.047, respectively). For each readmission, the mean length of stay was 10.7±2.5 days and the mean cost was $13,397±3,381. The cumulative number of hospital days during the 6 months post-discharge was 17.7±3.5 days for each readmitted patient and the mean per-patient total cost was $23,262±5,478. The mortality rate among readmitted patients was 13.2%. Overall, readmissions following AAA repair accounted for a cost >50% over and above the cost of the readmitted patients index hospitalization. Hospital readmissions are common during the 6 months following AAA repair. Patients who are readmitted experience long lengths of stay and high mortality rates, and their care incurs high costs.Dr. Eisenberg is a Physician-Scientist of the Quebec Foundation for Health Research. Dr. Pilote is a Physician-Scientist of the Canadian Institutes for Health Research.     

Wear of ultra-high-molecular-weight polyethylene cup articulating with 22.225 mm zirconia diameter head in cemented total hip arthroplasty

A number of studies have highlighted the increasing incidence of aseptic cup loosening with increasing depth of cup penetration by the metal head. We present our experience with a 22.225mm diameter zirconia head on a 9–10 taper articulating with an ultra-high-molecular-weight polyethylene (UHMWPE) cup in cemented total hip arthroplasties. We prospectively studied the wear of the UHMWPE cup articulating with a 22.225mm diameter zirconia head in cemented total hip arthroplasties. A total of 339 patients (153 men, 186 women, 373 hips) were included. The patients mean age at surgery was 52 years (17–76 years), with 41% age 50 years or younger. Their mean weight was 72.4kg (24–125kg). At a mean follow-up of 4.3 years (0–8 years) the mean penetration rate of the cup was 0.03mm/year (0–0.51mm/year). Altogether, 289 (77.5%) showed no measurable wear, 38 (10.2%) had a penetration rate of 0.11mm/year or less, 33 (8.9%) had a rate of 0.12–0.2mm/year, and in 13 (3.5%) the rate was more than 0.2mm/year. Ceramic–UHMWPE is the next stage in the evolution of total hip arthroplasty for addressing wear and any possible related issues.     

Quantitative determination of atracurium in human plasma using high-performance liquid chromatography

The authors have established a new method for extraction and determination of atracurium in human plasma that employs a reversed phase high-performance liquid chromatography (HPLC). This method made use of a fluorescent spectrophotometer at an excitation wavelength of 240nm and an emission wavelength of 310nm. The mobile phase was made of a phosphate buffer, distilled water and acetonitrile (20V:30V:50V). The analytical column used was a Little Champ C₁₈.In a Bond Elute C₁₈ extraction column, which had been prewashed with a phosphate buffer and a 50% methanol solution, atracurium was extracted from acidified plasma samples using a mixture of methanol and phosphate buffer. A standard curve was prepared by the internal standard method using metocurine. A high linear correlation between atracurium concentration and the ratio of the atracurium peak height to the metocurine peak height was observed (r = 0.9994). The lowest threshold for detection of atracurium was 15ng/ml. When the plasma concentrations of atracurium were determined in 2 clinical cases, t_1/2 was 2.10 and 1.73min and t_1/2 was 15.57 and 21.57min, respectively. These results indicate that this method of extraction and determination is appropriate for studying the pharmacokinetics of atracurium because it allows a high reproducibility, and provides an extremely accurate, simple and quick analysis.(Okutani R, Kono K, Frederic M. deBros et al.: Quantitative determination of atracurium in human plasma using high-performance liquid chromatography. J Anesth 2: –, 1988)     

EnHurane supresses phrenic nerve-diaphragm Transmissionin vivo

We examined the effects of enflurane on the diaphragmatic function in 15 pentobarbital-anesthetized, mechanically ventilated dogs. They were divided into three groups of five animals each, according to the administered concentration of enflurane. The diaphragmatic function was assessed from transdiaphragmatic pressure (Pdi) and integrated diaphragmatic electromyography (Edi) developed at functional residual capacity against an occluded airway during bilateral supramaximal phrenic nerve stimulation at 0.5, 10, 20, 50 and 100Hz under quasiisometric condition. After a control measurement, enflurane was administered at a constant end-expired concentration (0, 0.5 and 1MAC) and the measurement was repeated after 1 hour of exposure. The Pdi amplitude generated by single twitch (0.5Hz) and during 10, 20 and 50Hz stimulation was unchanged between the groups. No change in Pdi during 100Hz stimulation was noted during 0 and 0.5MAC exposure, while it was reduced by 1MAC of enflurane. When the values of Pdi were expressed as % of maximum Pdi (%Pdi,max) that developed during control measurement and analyzed in terms of %Pdi,max—stimulus frequency relationship, a significant decrease in %Pdi,max was noted for 100Hz stimulation in 0.5 and 1MAC groups compared to the control. Similarly, Edi during 100Hz stimulation obtained in 0.5 and 1MAC groups was markedly depressed compared to the control. Edi during 50Hz stimulation was also decreased at 1MAC. Relative changes in Edi following enflurane administration were greater than the corresponding changes of Pdi. These results demonstrate that enflurane impairs diaphragmatic function through its inhibitory effects on neuromuscular transmission.(Kochi T, Ide T, Isono S, et al.: Enflurane supresses phrenic nerve-diaphragm transmission in vivo. J Anesth 5: 260–267, 1991)     

Suppression of parathyroid hormone secretion in CAPD patients by intraperitoneal administration of Maxacalcitol

Background Maxacalcitol (22-oxacalcitriol; OCT) is a novel vitamin D analogue. In previous clinical studies, OCT was administered three times a week to hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in whom it acted by inhibiting parathyroid hormone secretion, as well as causing mildly elevated serum calcium. However, intravenous injection of OCT, which requires frequent visits to the outpatient clinic, degrades the quality of life of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise visit the clinic only once or twice per month. In the present study, we investigated whether transperitoneal absorption of OCT inhibited intact parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the peritoneal dialysis fluid.Methods Peritoneal dialysis fluid containing 20µg of OCT was injected into the peritoneal cavity of five CAPD patients. The serum and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured before and after treatment.Results The mean concentration of OCT in peritoneal dialysis fluid rapidly decreased, from 25268.0pg/ml at 0h to 1694.0pg/ml at 2h and 44.9pg/ml at 4h. In contrast, the mean serum OCT level increased from the pretreatment level, which was below the detection limit of the assay, to 656.0pg/ml at 0.5h and a peak of 759.0pg/ml at 1h, and thereafter gradually decreased, to 713.8pg/ml at 2h and 555.8pg/ml at 4h. Mean i-PTH significantly decreased, to 83.9% of the baseline level, at 1h (P < 0.05) and thereafter stayed at around 90%. No consistent trends in calcium and phosphate levels were observed in the five patients.Conclusions By injecting OCT into the peritoneal cavity, i-PTH levels could be significantly decreased. These findings indicate the therapeutic efficacy of intraperitoneal administration of OCT for CAPD patients.     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

Effects of thiopental on cardiac energy metabolisms in postischemic reperfusion in rat

In experiments on isolated rat heart lung preparation, the effects of thiopental on myocardial metabolisms in postischemic reperfusion were evaluated with intramyocardial high energy phosphates, lactate, pyruvate and glycogen. The release of CPK in the perfusate blood was also measured at the end of reperfusion. After 10min perfusion, hearts were made globally ischemic for 8min and reperfused for 12min. Large dose of thiopental (100µg/ml) reduced the energy charge and glycogen content. Reperfusion with an anesthetic dose of thiopental (10µg/ml) resulted in an exacerbation of the CPK release. Protection by thiopental during ischemia was not observed and its high dose may be harmful.(Kashimoto S et al.: Effects of thiopental on cardiac energy metabolisms in postischemic reperfusion in rat. J Anesth 1: 77–81, 1987)     

Brain lesion size and phase shift as an index of cerebral autoregulation in patients with severe head injury

Summary ¶Background. Whether the phase relationship (phase shift) between cerebral blood flow velocity as assessed by transcranial Doppler ultrasound and blood pressure at 0.1Hz can be used to assess cerebral autoregulation (CA) in patients with severe traumatic brain injury (TBI). Methods. In 33 healthy volunteers (mean age, SD; 37±17 years, range 17–65) middle cerebral artery (MCA) blood velocity (V) was recorded simultaneously with finger blood pressure (BP) over a period of 10 minutes under normocapnic and hypocapnic conditions to generate normative data. In 27 patients with severe TBI (Glasgow Coma scale score 8) serial close in time investigations of cranial computed tomography (CT) scanning and phase shift assessment were performed on days 1, 3, 5, and 8 after trauma. Phase shift in the MCA was compared to brain parenchyma lesion size in the MCA territory on CT scanning. Lesion size was classified into 0, normal; 1, presence of a small lesion (diameter <3cm); 2, presence of a large lesion (>3cm). Findings. Compared to normocapnia, hypocapnia significantly increased phase shift at 0.1Hz from 78±28° to 101±25° (p<0.001). In the TBI patients, 115 comparisons between CT findings and CA results were possible. Phase shift detected a pathological CA in 31 instances, which were more frequent in CT lesion type 2 (19/42) than in group 0 (7/44) and group 1 (5/29). Interpretation. When CA is intended to be assessed by use of phase shift, the hyperventilation setting needs its own reference values. In MCA territories containing a traumatic lesion greater than 3cm in diameter phase shift at 0.1Hz will detect a high frequency (44%) of a disturbed state of CA.Published online July 23, 2003     

Combined effects of Inversed Ratio Ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure

Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure (PEEP) on cardiorespiratory function were examined in 24 patients with acute respiratory failure. Patients were divided into two groups: the IRV group (n = 12) who showed no significant increase in Pa_{O 2} with a 6cmH₂O of PEEP and PEEP group (n = 12) who were ventilated mechanically with PEEP only at maximum level of 10cmH₂O. In IRV group step-wise prolongation of the I:E ratio from 1:1.9 to 2.6:1 or 4:1 was applied as a Pa_{O 2} was improved and in PEEP group also level of PEEP was increased from 0, 5 to 10cmH₂O after one hour period irrespective of Pa_{O 2}. Inversed ratio ventilation and PEEP increased significantly Pa_{O 2}/Fi _{O 2}, the increase being observed 6hrs (I:E = 2:1) and 2hrs (10cmH₂O) after starting IRV or PEEP. Further improvement of oxygenation was not observed in IRV even if I:E ratio was prolonged up to 2.6:1 or 4:1. These results suggested that combinations of IRV with PEEP were effective and an I:E ratio of 2:1 may be optimal, and IRV is advantageous compared to PEEP, but will take more long time to improve oxygenation than PEEP.(Sari A, Toriumi T, Yamashita S, et al.: Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure. J Anesth 5: 105–113, 1991)     

Addition of epinephrine to intrathecal tetracaine augments depression of the bispectral index during intraoperative propofol sedation

Purpose Epinephrine added to local anesthetic agents for spinal anesthesia is frequently used to prolong the duration of anesthesia. Epinephrine stimulates the -adrenoceptor, and it is known that the 2-adrenoceptor agonists have a central inhibitory effect. We investigated the effect of intrathecal epinephrine during propofol sedation with spinal anesthesia, using a bispectral index (BIS) monitor.Methods Twenty adult patients, scheduled for spinal anesthesia, were allocated to the control group (n = 10) or epinephrine group (n = 10). Patients in the control group received 14mg of tetracaine, whereas the epinephrine group received 14mg of tetracaine and 0.2mg of epinephrine. Immediately after the pinprick test, propofol was administered at 0.5mg·kg^–1 by infusion for the initial dose, then continuously at 2mg·kg^–1·h^–1 in both groups. BIS scores were recorded before subarachnoid block, and then every 5min for 90min after subarachnoid block.Results There were significant differences in the BIS score between the two groups at 45–55min and at 60–70min after subarachnoid block.Conclusion Intrathecal epinephrine augments the sedative effect of propofol during spinal anesthesia.     

Beneficial Effects of Apolipoprotein A-I on Endotoxemia

Purpose. Although many studies have shown the beneficial effects of lipoproteins on animals with endotoxemia, little is known about the impact of apolipoprotein A-I (apoA-I) on tumor necrosis factor (TNF-) release in response to lipopolysaccharide (LPS). The present study was conducted to determine whether the administration of apoA-I inhibits the release of TNF- and influences the survival rate of rats with endotoxemia.Methods. Forty male Wistar rats were divided randomly into four groups. Rats in the first and second groups were given 1mg/kg LPS intraperitoneally (i.p.) and blood was collected 1h later to measure the serum levels of TNF-. Either 10mg/kg apoA-I or Tris-buffered saline was injected i.p. and the serum TNF- levels were measured again 2h later. Rats in the third and fourth groups were given 5mg/kg LPS. Following the administration of 10mg/kg apoA-I or Tris-buffered saline, animals were observed for 5 days and survival rates were determined.Results. ApoA-I inhibited the release of serum TNF- and improved the survival rates of rats with endotoxemia.Conclusion. The administration of apoA-I suppressed the TNF- release in endotoxemia and decreased the mortality rates of rats.     

The effects of calcium antagonists on EEG,evoked potentials and neurologic recovery after complete global brain ischemia for 15 minutes in dogs

The effects of three calcium antagonists on the recovery from neurologic damages after complete global brain ischemia were examined by evaluating the change of a electroencephalogram (EEG), evoked potentials (EP) and a neurologic recovery score (NRS) in dogs. Fifteen minutes global brain ischemia was achieved by occluding the ascending aorta and the caval veins. Nicardipine (NC), flunarizine (FL) and diltiazem (DL) were administered with continuous infusions for three days after the ischemia. The EEG-EP scores (0:no response – 6:normal) 3hr after the ischemia were 1.4 ± 0.4 (mean ± SE) in the control, 2.2 ± 0.3 in the NC, 2.2 ± 0.4 in the FL and 2.1 ± 0.2 in the DL. There were no significant differences between the 4 groups. The survival rates on the 7th day after the ischemia were 67% (6/9) in the control, 78% (7/9) in the NC, 56% (5/9) in the FL and 89% (8/9) in the DL. No significant differences were presented between the 4 groups. The NRSs (0:death – 100:normal) on the 7th day were 40.3 ± 7.3 in the control, 59.0 ± 8.5 in the NC, 63.2 ± 9.7 in the FL and 55.7 ± 3.3 in the DL. Each treated group showed a tendency to have a higher NRS than that in the untreated control group. The NRS in all dogs treated by the Ca⁺⁺ antagonists on the 7th day was 58.7 ± 4.1, which was significantly higher than that in the control group (P < 0.05). We conclude that the continuous administration of calcium antagonists for three days after the global brain ischemia would be beneficial for the neurologic recovery.(Ono K, Iwatsuki N, Takahashi M, et al.: The effect of calcium antagonists on EEG, evoked potentials and neurologic recovery after complete global brain ischemia for 15 minutes in dogs. J Anesth 5: 114–122, 1991)     

Secondary growth of a cortical necrosis: effect of NOS inhibition by aminoguanidine post insult

Summary ¶Background. A cortical tissue necrosis from a focal freezing injury expands to 140% of its initial volume within 24hrs in rats. Previous studies of our laboratory have shown that administration of the NOS inhibitor aminoguanidine (AG) prior to trauma attenuates this process of secondary brain damage. Objective of the present study was to analyse whether this agent is also protective when treatment commences after the insult. Method. A highly standardized freezing lesion was induced in the brain cortex of 30 anaesthetized rats. The animals were divided into three experimental groups. Animals of group I (sham-5min, n=10) were sacrificed 5min after trauma for quantitative histomorphometric assessment of the primary cortical lesion. Animals of group II (sham-24h, n=10) received isotonic saline (16.7ml/kg b.w., i.p.) at 15min and 8hrs after trauma. In the treatment group (group III, AG-24h, n=10), AG was administered (100mg/kg b.w.) also at 15min and 8hrs after trauma. 24hrs later – the time point of maximal lesion spread – the animals of group II and III were sacrificed for quantification of the secondary lesion growth. Findings. The focal freezing injury produced a cortical necrosis volume of 6.07±1.04mm³ immediately after trauma (group I). After sham treatment, the necrosis expanded to 8.39±1.57mm³ within 24hrs (group II) corresponding to a lesion growth of 138% compared to the primary necrosis (p<0.01 vs. group I). In animals treated with AG after the trauma (group III), the volume of necrosis was significantly attenuated at 24hrs to 6.77±0.87mm³ representing an expansion of the lesion to only 112% (p<0.05 vs. group II). Thus, AG was inhibiting the secondary growth of necrosis by no less than 69%. Interpretation. The findings demonstrate that AG retains its neuroprotective potential against secondary brain damage from trauma even when administration begins after trauma.Published online October 20, 2003