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.     

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.     

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.     

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)     

AneuRx Device Migration: Incidence, Risk Factors, and Consequences

Success after endovascular abdominal aortic aneurysm repair (EVAR) is dependent on device positional stability. The quest for such stability has motivated different endograft designs, and the risk factors entailed remain the subject of debate. This study aims at defining the incidence, risk factors, and clinical implications of device migration after EVAR with the AneuRx® endograft. In this study we included all consecutive 109 patients submitted to primary AneuRx placement for infrarenal aortic or aortoiliac aneurysms. Preoperative computed tomography (CT) scans were reviewed for the following anatomic characteristics: neck length, diameter, angulation, calcification, and thrombus load; and sac diameter and thrombus load. Percentage of device oversizing relative to the proximal neck diameter was determined. All postoperative CT scans were reviewed, and the distance between the lowest renal artery and the craniad end of the device was measured. A 5-mm increase in such distance was considered indicative of device migration. Migration cumulative incidence was estimated by the Kaplan-Meier method, and its association with any of the preoperative anatomical characteristics was tested using Cox proportional hazards models. Median follow-up time was 9 (range, 1-31) months. Migration occurred in nine patients, corresponding to a 15.6% estimated probability of migration at 30 months (SE=5.1%). Migration was associated with the risk of proximal type I endoleak (hazard ratio=3.39, 95% confidence interval=1.46-7.87; p=0.007). This type of endoleak occurred in three of the migration-affected patients (33.3%); all of them were resolved by additional cuff placement at the proximal landing zone. No other migration-related reinterventions were performed. The only significant associations between anatomic factors and device migration probability were the protective effects of longer necks (odds ratio [OR]=0.71 for each additional 5 mm, p=0.045) and longer overlapped portions of neck and device (OR=0.56 for each additional 5 mm, p=0.003). There was a trend toward higher probability of migration among reverse-tapered necks (OR=1.75, p=0.109). Percentage of device oversizing correlated with early neck dilation (between preoperative and first postoperative diameters, correlation coefficient=0.4, p < 0.0001), but not with late neck dilatation (between first postoperative and 1.5-year scan diameters, correlation coefficient=0.29, p=0.112). There was a trend toward higher mean percentage of late dilation among migrators (11.4%, standard error of the mean [SEM] 2.6) than nonmigrators (5.7%, SEM=1) (p=0.08), but both groups had similar mean percentages of early dilation (3%, SEM=1.6%, vs. 5.5%, SEM=0.6%; p=0.365). This result indicates that device migration is not a rare event after AneuRx implantation. This phenomenon is associated with proximal type I endoleaks. Deployment of the endograft immediately below the renal arteries might help to prevent migration, since use of greater lengths of overlapped device relative to the proximal neck has a protective effect. Migration seems to be independent of the degree of device oversizing.Presented at the 29th Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, Sergio M. Sampaio is a recipient of the Edward S. Rogers Clinical Research Fellowship in Vascular Surgery.     

Effects of Cilostazol on Human Venous Smooth Muscle

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10^–2 M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 g/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15±1.9% (mean±SEM) at low cilostazol doses (680 g/L) to 37±3% at high cilostazol doses (2,720 g/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n=52) or hypercholesterolemia (n=18) did not affect the amount of relaxation of the venous rings. Smokers (n=46) had less relaxation 16±2.4% (680 g/L) to 41±3.6% (2,720 g/L) compared to nonsmokers (n=53) who relaxed 22±3.5% (680 g/L) to 48±5.7% (2720 g/L). This did not reach statistical significance at any concentration cilostazol (p=0.11-0.18). Diabetics (n=53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n=11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.     

Dose-finding study of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam

Purpose We investigated the effective and safe dose of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam.Methods One hundred and eighty patients aged 20–50 years scheduled for spinal anesthesia received midazolam 0.06mg·kg^–1 and atropine 0.01mg·kg^–1 intramuscularly 15min before entering the operating room. Spinal anesthesia was performed with 0.5% hyperbaric tetracaine. Five minutes after starting surgery, midazolam 0 (control group), 0.01, 0.02, 0.03, 0.04, or 0.05mg·kg^–1 was intravenously administered (30 patients each). Blood pressure, heart rate, respiratory rate, percutaneous oxygen saturation (S_{p O 2}), verbal response, eyelash reflex, and involuntary body movement were measured every 5min for 30min. Memory during surgery was also investigated.Results The number of the patients with loss of verbal response, with loss of eyelash reflex, and with no memory during surgery were significantly larger in the groups receiving midazolam 0.03mg·kg^–1, 0.04mg·kg^–1, and 0.02mg·kg^–1, respectively. The decrease in blood pressure or increase in respiratory rate with decrease in S_{p O 2} was significantly larger in the groups receiving midazolam 0.03mg·kg^–1 or 0.05mg·kg^–1, respectively.Conclusion For sedation and amnesia of the patients aged 20–50 years in spinal anesthesia with about 1h duration receiving intramuscular midazolam 0.06mg·kg^–1 as a premedication, intravenous midazolam 0.02mg·kg^–1 might be effective and safe.     

Safety of Contrast Venography prior to Caval Interruption in Patients with Renal Insufficiency

We undertook this study to determine whether the use of contrast venography would adversely affect renal function in patients with renal insufficiency requiring caval interruption. We conducted a retrospective review of all inferior vena cava (IVC) filters inserted at our institution over a 2-year period (January 2002 to January 2004). The indication for caval interruption, insertion technique, type of filter used, pre- and postintervention creatinine level, and the presence of diabetes and hypertension were analyzed. A total of 282 IVC filters were inserted, with 38 of them placed in patients with renal insufficiency as defined by a serum creatinine level of > 1.5 mg/dL. Contrast venography with 15 to 30 mL of iohexol (Omnipaque 300) was used in all cases, and no special measures other than proper hydration were used for renal protection. All filters were successfully deployed. The mean±SD preintervention creatinine level was 2.38±0.79 mg/dL. The mean±SD postintervention creatinine levels at 2 and 30 days were 2.26±0.45 mg/dL and 2.12±0.94 mg/dL, respectively. No patients required hemodialysis following caval interruption, and no adverse effect on renal function was noted. Contrast venography accurately delineates venous anatomy and facilitates proper caval filter placement with no apparent adverse effect on renal function. We believe contrast venography is safe even in the presence of renal insufficiency.     

Long-term results of rotational total hip arthroplasty: radiological analysis

We developed a rotational total hip prosthesis that has a 30mm diameter metal-covered head with a polyethylene liner with which it can rotate around the neck of the stem. Long-term results of the rotational total hip arthroplasty with cement were evaluated in 55 hips of 52 patients. The diagnosis was degenerative osteoarthritis in all patients. The mean follow-up was 11.2 years (range 5–19 years). Eight of thirty 7mm thick acetabular components were revised 7.6–14.3 years (mean 10.4 years) afterward. Two of twenty five 9.5mm thick acetabular components and two femoral components were revised at 12 and 15 years, respectively. The mean polyethylene wear in the 9.5mm thick acetabular components was significantly less than that in the 7mm thick components. The mean polyethylene wear inside the rotational head removed during the revision surgeries was 0.01mm in diameter and 0.03mm in depth per year, respectively. Fifty percent of the patients with 7mm thick acetabular components, 9.5mm thick components, and femoral components had surviving prostheses at 13.4, 15.2, and 16.3 years, respectively. It is possible that the rotational system reduces the stress against acetabular and femoral components, but the 30mm diameter head caused high friction torque and required at least 9.5mm thickness in the acetabular component.     

Enhancement of lidocaine-induced epidural anesthesia by deoxyaconitine in the rabbit

Purpose.Aconiti tuber has been used in traditional Oriental medicine to alleviate pain. The antinociceptive property of aconiti tuber is due to the action of its extracted alkaloids such as deoxyaconitine. The purpose of this study was to investigate the effect of epidural deoxyaconitine on epidural lidocaine anesthesia. Methods.Five adult rabbits were used. Three different combinations of drugs were injected into the epidural space, in the following order: first (combination A), 1.5ml of 2% lidocaine; second (combination B), 1.5ml of 2% lidocaine and 150µg deoxyaconitine; and third (combination C), 3mg nor-binaltorphimine followed by 1.5ml of 2% lidocaine and 150µg deoxyaconitine 30min later. The latency of onset and the duration of three end-points (sensory loss in the tail, loss of weight-bearing ability, and flaccid paresis of hind limb) were measured. Results.Onset times for the three end-points were not changed by deoxyaconitine or by nor-binaltorphimine. The duration of sensory loss was 27.0 ± 2.7min, the duration of loss of weight-bearing ability was 33.0 ± 2.7min, and the duration of flaccid paresis was 21.0 ± 4.2min in the combination A group. In the combination B group, deoxyaconitine extended the time of sensory loss by 80%, the time of loss of weight-bearing by 50%, and that of flaccid paresis by 60% compared with the combination A group. In the combination C group, this phenomenon was partially antagonized by pretreatment with nor-binaltorphimine, a -opioid antagonist. Conclusions.Based on our observations, deoxyaconitine enhanced epidural lidocaine anesthesia in the rabbit, and this effect seemed to be partly mediated by -opioid receptors.     

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.     

Reduction in late postoperative pain after iliac crest bonegraft harvesting for cervical fusion: a controlled double-blinded study of 100 patients

Summary Background. A randomized prospective double-blinded study was conducted in 100 patients suffering from mono- or bisegmental cervical retrospondylosis or disc herniation.Method. In group I, 50 patients were treated by injection of 10ml Ropivacaine 7,5% at the iliac crest bonegraft donorsite. Local anaesthetic (LA) was injected through the wound drainage after closure of the muscle fascia, the suction drainage was opened after closure of the skin. Group II was treated with 0,9% saline. Operator and patient were blinded to the injected substance. Daily controls of pain intensity were made with the 10cm visual analog scale from 0 (no pain) to 10 (severe pain) for 5 days. All patients were questioned regarding pain character and movement provoking pain. Additional pain medication was standarized.Findings. Statistical analysis of mean pain intensity over the whole hospital stay showed a significant difference in pain intensity between the two groups (p=0,017, Chi-Square test). The comparison between pain intensity with LA and without LA showed a gradual increase in statistical significance from day 1 to day 5 (day 1: p=0,54, not significant; day 2: p=0,026; day 3: p=0,008; day 4: p=0,004; day 5: p=0,002).Interpretation. This data shows that intra-operative blockage of peripheral nociceptive structures results in decreased pain at later time points. We conclude that wound infiltration with 7,5% Ropivacaine after bonegraft removal at the iliac crest is effective in reducing postoperative pain.     

Percutaneous and Open Renal Revascularizations Have Equivalent Long-Term Functional Outcomes

Atherosclerotic renal artery stenosis is a significant cause of poorly controlled hypertension and progressive renal dysfunction leading to ischemic nephropathy and other end-organ damage. The optimal treatment of renovascular disease contributing to hypertension and renal dysfunction is not known. This study compares the anatomic and functional outcomes of both open and endovascular therapy for chronic, symptomatic atherosclerotic renal artery disease. We performed a retrospective analysis of records from patients who underwent renal arterial interventions, endovascular or open bypass, between January 1984 and January 2004. Principal indications for intervention were hypertension (51%), chronic renal insufficiency (13%), and hypertension and elevated creatinine (36%). A total of 247 patients (109 males; mean age 69±10, range 44–89 years) underwent 314 interventions (109 open procedures; 205 angioplasties, 71% with stent placement). There was a significant difference in 30-day mortality (4% vs. <1%; p < 0.005) between the open and endoluminal groups, but not at 1, 3, or 5 years. Patients in the open group had a higher primary patency rate at 5 years (83±5% vs. 76±6%; p=0.03), but patients in the endoluminal group had a higher assisted primary patency rate at 5 years (92±5% vs. 84±5; p=0.03). There was no significant difference between both treatment groups in cumulative freedom from presenting symptom or in freedom from dialysis and renal-related death. Patients who presented with hypertension were more likely to have shown improvement in their blood pressure with endoluminal intervention at 1, 3, and 5 (59±6% endoluminal vs. 83±5% open; p=0.01) years. From these results we conclude that open repair and endoluminal repair of atherosclerotic renal artery stenosis have similar immediate and long-term functional and anatomic outcomes. Patients who present with hypertension may have greater benefit with an endoluminal repair.Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004.     

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)     

Erythemas caused by electrodes while monitoring neuromuscular blockade: three cases

Skin erythemas formed in three patients during surgery at the sites where negative electrodes had been attached to stimulate the ulnar nerve for a neuromuscular transmission monitor (Relaxograph). The patients were all women, aged 52, 62, and 74 years, and general anesthesia lasted 8h 20min, 4h 50min, and 8h 45min, respectively. The electrodes used were disposable ECG electrodes in the first two patients and one designed for a neuromuscular monitor in the third; all were carbon-coated and then covered with gel. However, when the electrodes were detached from the lesion, they all showed loss or damage of the carbon coating under the gel. We recommend balancing the merit of monitoring with the risk of complications, even when applying an apparently safe, noninvasive monitor.     

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)     

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)     

Enzyme inhibition by analgesic and hypnotic agents on anaerobic dehalogenation of halothane

Enzyme inhibition on anaerobic dehalogenation of halothane by various analgesic or hypnotic agents was investigated in vitro using rat liver microsomal fraction. The production rate of chloro-difluoro-ethylene (CDE) and chloro-trifluoro-ethane (CTE), anaerobic metabolites of halothane, was measured when various concentrations of analgesic or hypnotic agents (fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine and hydroxyzine) were supplemented. Inhibitor constant (Ki) of each agent was calculated and compared with each other. The activity of NADPH-cytochrome c reductase (fp₂) and NADH-ferricyanide reductase (fp₁) was measured when each agent was added. The values of inhibitor constants (Ki) for CDE and CTE formation were in the following order from large to small values; morphine (656µM and 2570µM), chlorpromazine (49.7µM and 68.1µM), ketamine (24.9µM and 64.4µM), fentanyl (23.9µM and 34.6µM), hydroxyzine (19.2µM and 50.8µM), diazepam (17.0µM and 13.9µM), buprenorphine (11.2µM and 22.4µM), and pentazocine (1.96µM and 6.67µM) respectively. Pentazocine inhibited the formation of CDE 300 fold greater than morphine. The activity of fp₂ and fp₁ did not change by the addition of these analgesic or hypnotic agents. These results indicate that various analgesic or hypnotic agents, which are commonly used with halothane in clinical anesthesia, suppress the anaerobic dehalogenation of halothane in vitro. They also imply that the suppression of production of halothane metabolites is the result of direct enzyme inhibition on cytochrome P-450, since these agents did not affect the activity of fp₂ and fp₁ which are flavoproteins existing in the microsomal electron transport system.(Yamanoue T, Kikuchi H, Fujii K, et al.: Enzyme Inhibition by Analgesic and Hypnotic Agents on Anaerobic Dehalogenation of Halothane. J Anesth 5: 331–337, 1991)     

Analgesic dose-response relation in cervical epidural block

The relationship between the age and the spread of analgesia from different epidural anesthetic doses was examined by studying analgesic dose responses in cervical epidural analgesia. Two different anesthetic doses (5ml or 10ml) of 2% mepivacaine were injected into the cervical epidural space at a constant pressure (80mmHg) using an intravenous apparatus, and the spread of analgesia to pinprick was assessed. The significant correlation was found between the patients age and the number of spinal segments blocked (5ml:r = 0.8498, P < 0.01, 10ml:r = 0.5988, P < 0.01). The inverse linear relationship was found between the patients age and the segmental dose requirement (5ml:r = –0.6754, P < 0.01, 10ml:r = –0.5784, P < 0.01). Patients under 39 years of age showed a direct relationship between the dose injected and the number of spinal segments blocked, enabling prediction of the number of segments blocked with a given dose of local anesthetic. Doubling the epidural dose approximately doubled the number of spinal segments blocked. The analgesic dose-response relation in patients over 60 years of age differed from that in patients under 39 years of age and doubling the epidural dose did not double the number of spinal segments blocked. Progressively more extensive analgesia was obtained from a given dose of local anesthetic with advancing age. It was difficult to limit the extent of analgesia by injecting a smaller dose of local anaesthetic in the elderly.(Hirabayashi Y, Matsuda I, Inoue S et al.: Analgesic dose-response relation in cervical epidural block. J Anesth 2: 22–27, 1988)     

Treatment outcomes and mortality of 94 patients with acromegaly

Summary Background. Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003.Method. The cohort consisted of 94 patients who had been followed for 0.3–31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0µg/l and a random GH value of <2.5µg/l.Findings. Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1cm), 65% with meso-adenomas (1cm to <2cm) and 27% with macro-adenomas (2cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin^® LAR^®) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2cm. The standardized mortality ratio was 1.30 (95% CI 0.52–2.67) for patients in remission and 1.38 (95% CI 0.51–3.00) for patients with persistent acromegalic activity.Conclusions. Most patients with adenomas of <2cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2cm and more than 80% of patients with adenomas of 2cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.