Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis

Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4‐h intravenous infusion of LPS (total dose: 2 ng kg^?1). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh‐cuff deflation‐induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh‐cuff deflation caused a MAP reduction of 16 (13–20) % at baseline and 18 (16–20) % after LPS, while the MAP reduction was 12 (11–13) % in patients (P<0·05 versus volunteers at baseline; P<0·01 versus volunteers after LPS). The corresponding RoR values increased from 0·46 (0·31–0·49) s^?1 at baseline to 0·58 (0·36–0·74) s^?1 after LPS (P<0·05) in healthy volunteers, whereas they were similar to values observed in patients [0·43 (0·36–0·52) s^?1; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh‐cuff deflation failed to induce sufficient MAP reductions in patients.     

The use of propofol sedation in a paediatric intensive care unit

Background: The aim of this study was to prospectively evaluate and report the experience of the use of continuous intravenous propofol sedation in a paediatric intensive care unit (PICU). Methods: All children younger than 16 years who were admitted to the PICU at a University Hospital for slightly more than a year and received propofol infusion were included prospectively and data were recorded before and within 6 h after completion of the propofol infusion. Results: A total of 174 out of 955 children (18·2%) received propofol infusion for sedation. The median age was 2 years 10 months (range: 2 months to 16 years), duration of propofol infusion 13 h (range: 1·6–179 h) and dose of propofol 2·9 mg/kg/h (range: 0·3–6·5 mg/kg/h). No one developed signs of the propofol infusion syndrome (PRIS). Neither dose >3 mg/kg/h, duration of infusion >48 h nor both were found to be related to adverse metabolic derangements or circulatory failure. Eight children increased their lactate concentration ≥1·8 mmol/L during propofol infusion. All had a favourable outcome. One child who had received propofol infusion for 10 h died, but this occurred 14 h after the infusion ceased and was without doubt attributed to a multiple organ failure not related to the propofol infusion. Conclusion: Propofol infusion was used in this population at low risk of PRIS with no metabolic or circulatory adverse effects. These findings indicate that the occurrence of adverse effects may not be directly related to dose or duration of infusion, but emphasizes the risk that sporadic factors may be involved, such as genetic mutations. Guidelines are presented.     

血管加压素对心肺转流术后血管麻痹综合征患者血流动力学的影响

目的评价血管加压素对心肺转流术(CPB)后血管麻痹综合征患者血流动力学的影响。方法选取CPB下心脏手术后发生血管麻痹综合征患者14例,分为去甲肾上腺素(NE)组(NE组)和血管加压素(AVP)组(AVP组)。NE组患者输注NE维持平均动脉血压>65 mmHg,当NE输注速率>0.4μg/(kg.min)则加用AVP 0.01～0.04 U/min;AVP组患者输注AVP0.01～0.04 U/min,必要时使用NE维持患者平均动脉血压>65 mmHg。于血管麻痹综合征诊断时(T1,基础值)、注药后24 h(T2)、48 h(T3)、72 h(T4)分别记录两组患者心率(HR)、平均动脉压(MAP)、平均肺动脉压(MPAP)、心排血量(CO)、肺毛细血管楔压(PCWP)、中心静脉压(CVP)及尿量,计算体循环血管阻力(SVR)及肺循环血管阻力(PVR)。并记录儿茶酚胺药物使用量及不良反应。结果两组患者年龄、体重、性别构成比,术前EF、术前治疗用药情况、CPB时间、主动脉阻断时间比较差异无统计学意义(P>0.05)。两组患者血压维持稳定。与NE组比较,AVP组SVR T2时增加;HR T2～3时显著降低(P<0.05);NE需要量T2～4明显降低(P<0.05);尿量明显增加(P<0.05)。结论 AVP可以改善CPB术后血管麻痹综合征患者的血流动力学。     

A modified thrombin clotting time test as a quality control marker for heparin contamination in obstetric intraoperative cell salvage

Objective: To assess if a modified thrombin clotting time test could be used as a simple quality control (QC) method to screen for unfractionated heparin in the product obtained from obstetric intraoperative cell salvage cases before re‐infusion. Background: A national QC scheme has recently been piloted to monitor the quality of autologous blood being returned to the patient. Laboratory tests include full blood count and microalbumin. Unfractionated heparin testing should be performed to ensure that there is no gross contamination of heparin in the final product; however, presently, there is no quick cheap test available suitable for heparin detection. Materials and Methods: Samples were collected into plain non‐anticoagulated tubes and centrifuged at 2500 ×g for 5 min. Supernatant was mixed with commercially available coagulated normal plasma and a thrombin clotting time test performed. Results: Calibration runs demonstrated that our system was sensitive up to 0·14 IU mL^?1 heparin, linear between 0·08 and 0·14 IU mL^?1. Conclusion: We have shown that the thrombin clotting time test can be modified and used as a cheap and reliable marker for heparin contamination. We have successfully incorporated this modified test into our hospital's obstetric QC scheme.     

Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep

Objective: The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep. Design: 12 sheep were instrumented for chronic study. Six sheep received l ^G-nitro-arginine-methylester (l-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h). Measurements and results: Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of l-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of l-NAME increased mean arterial pressure (MAP) from 76.1 ± 4.2 mmHg to normal values of 95.8 ± 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 ± 3.0 to 88.6 ± 4.7 mmHg (p < 0.05). This increase in MAP was associated in the l-NAME group with a more prominent drop in cardiac index (from 10.2 ± 0.4 to 7.0 ± 0.5 l · min^–1· m^–2; p < 0.05) than in the PHP group (from 10.7 ± 0.2 to 9.3 ± 0.6 l · min^–1· m^–2). During the first 90 min of infusion, cardiac index remained lower in the l-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the l-NAME group. Conclusion: These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with l-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated. Received: 29 January 1997 Accepted: 23 October 1997     

清开灵治疗小儿上呼吸道感染疗效观察

目的:探讨清开灵治疗小儿上呼吸道感染的临床效果。方法:将112例上呼吸道感染患儿随机分治疗组56例,采用清开灵20mg/(kg·d)一次静滴;对照组56例采用病毒唑10mg/(kg·d)一次静滴。2组其他综合治疗相同。结果:总有效率:治疗组94.6%,对照组82.1%,P<0.05;平均热退时间:治疗组(3.58±1.05)d,对照组(4.15±1.24)d,P<0.01;住院时间:治疗组(6.04±1.52)d,对照组(7.16±1.95)d,P<0.01。结论:清开灵治疗小儿上呼吸道感染疗效比病毒唑好。     

Daily interruption of sedative infusions in an adult medical–surgical intensive care unit: randomized controlled trial

Title. Daily interruption of sedative infusions in an adult medical–surgical intensive care unit: randomized controlled trial. Aim. This article is a report of a study conducted to determine if a nursing‐implemented protocol of daily interruption of sedative infusions vs. sedation as directed by the intensive care unit team would decrease duration of mechanical ventilation. Background. Continuous rather than intermittent infusion of sedative and analgesic agents leads to greater stability in sedation level, but has been correlated with prolongation of mechanical ventilation and hospitalization of critical care patients. Daily interruption of sedative infusions in mechanically ventilated patients has reduced the duration of mechanical ventilation and length of stay in intensive care. Method. A randomized controlled trial was carried out from November 2004 to March 2006 with 97 patients receiving mechanical ventilation and continuous infusion of sedative drugs in an intensive care unit in Greece. The primary outcome measure was the duration of mechanical ventilation. Secondary outcomes were length of intensive care unit stay, length of hospital stay, overall mortality, total doses of sedative and analgesic medicines and Ramsay scores and duration of cessation of sedative infusions per day. Results. The median duration of mechanical ventilation was 8·7 days vs. 7·7 days (P = 0·7). Length of intensive care unit stay (median: 14 vs. 12, P = 0·5) and in the hospital (median: 31 vs. 21, P = 0·1) was similar between the intervention and control groups. The absence of statistically significant differences in these variables remained when patients with brain injury were examined separately. Conclusion. The nursing‐implemented protocol of daily interruption of sedative infusions was neither beneficial nor harmful compared with usual practice, which has as its primary target the earliest possible awakening of patients.     

Naloxone in the management of hepatic encephalopathy

Background/aim: This study aimed to assess the effectiveness and safety of naloxone in the management of hepatic encephalopathy (HE). Methods: Cochrane collaboration methodology was used in a meta‐analysis of randomized controlled trials of naloxone therapy for HE. Results: Seventeen randomized trials were identified with 15 studies involving 1054 patients meeting criteria for inclusion. Naloxone use was associated with a significant improvement in HE [relative risk (RR) 1·46; 95% confidence interval (CI) 1·27–1·67; P = 0·0005]. This comparison showed statistical heterogeneity (P < 0·10, and χ² = 44·93). Subgroup analysis indicated naloxone administered parenterally by intermittent or continuous infusions to be effective (RR 1·34; 95% CI 1·17–1·53; P < 0·0001). A significant in trials by infusion route (RR 1·42; 95% CI 1·19–1·69; P < 0·0001) interaction was observed. Conclusions: Naloxone may improve HE. However, published data are limited.     

Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

Aim: During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before and during leg exercise. Material and methods: Eight healthy male subjects were investigated twice in the fasting state: during 3 h infusion of octreotide [30 ng (kg min)^?1] or sodium chloride with exercise at 50% of maximal VO₂ in the last hour. Glucose uptake and oxygen uptake in the leg were measured using Fick’s principle by blood sampling from an artery and a femoral vein. Blood flow in the leg was measured using the indicator (indocyanine green) dilution technique. Results: After an initial decrease during rest, octreotide infusion resulted in a significant increase in arterial glucose concentrations compared to control conditions during exercise (mean ± SEM: 7·6 ± 0·6 versus 5·6 ± 0·1 mmol l^?1, P<0·01). During rest, octreotide did not change the leg glucose uptake (59 ± 10 versus 55 ± 11 μmol min^?1). In contrast, leg glucose uptake was significantly lower during exercise compared to control conditions (208 ± 79 versus 423 ± 87 μmol min^?1, P<0·05). During exercise, leg oxygen uptake was not different in the two experiments (20·4 ± 1·3 versus 19·5 ± 1·1 μmol min^?1). Conclusion: In conclusion, infusion of octreotide reduced leg glucose uptake during exercise, despite the same leg oxygen consumption and blood flow compared to control conditions. The hyperglycaemic effect of octreotide can partly be explained by the reduction in leg glucose uptake. Furthermore, the results suggest that a certain level of circulating insulin is necessary to obtain sufficient stimulation of glucose uptake in the exercising muscles.     

万汶与贺斯应用于急性高容量血液稀释的效果比较

目的：探讨万汶与贺斯应用于急性高容量血液稀释（AHH）临床效果。方法：择取手术患者40例，随机均分为万汶组和贺斯组，在术前分别输入万汶、贺斯各15ml／kg，观察稀释前（T0）、稀释后20min（T1）、稀释后1h（T2）、手术结束时（T3）的HR、CVP、MAP及化验Hb、Hct、凝血、电解质和血气分析等。并记录术中出入量。结果：2组术中出入量、HR、MAP、CVP、凝血、血气指标、电解质指标在组间和组内均无显著性。2组Hb、Hct随输液量的增加而渐下降，T1、T2与T0比较均有显著性（P〈0．05），2组之间的下降无显著性。结论：万汶、贺斯应用于AHH安全有效，二者之间无明显差异。     

Comparing the cumulative incidences of add‐on therapy among the major antihypertensive classes in 2531 Asian patients: a cohort study

Background: Published literature addressing the efficacy of different antihypertensive drug classes among Asian patients is scarce. Methods: This cohort study included all patients prescribed their first‐ever antihypertensive monotherapy without concomitant use of chronic medications in two primary care clinics in Hong Kong during 1990–2002. The incidence of add‐on therapy within 48 weeks because of suboptimal blood pressure control was evaluated and compared among different age and gender groups. Results and discussion: Among the 2531 patients, the incidence of add‐on therapy among users of angiotensin converting enzyme inhibitors (ACEI) was highest in young females (31·1%, 95% CI 22·2%, 40·0%, P < 0·001) and elderly females (18·0%, 95% CI 11·3%, 24·7%, P = 0·049) as compared with thiazide diuretics, beta‐blockers and calcium channel blockers. The incidence of add‐on therapy among young males (20·3%, 95% CI 11·1%, 29·5%; P > 0·50) and elderly males (12·5%, 95% CI 3·8%, 21·2%) was also highest with the ACEI than other drug classes although statistical significance was not reached. Conclusion: The incidence of add‐on therapy among first‐time antiypertensives appear to be significantly different between drug classes. This deserves further investigation.     

Taurolidine attenuates the hemodynamic and respiratory changes associated with endotoxemia

The purpose of this study was to determine if prereatment with taurolidine, a known anti-endotoxin agent, would attenuate the hemodynamic and respiratory responses associated with endotoxin induced lung injury in a large animal model in a randomized controlled study under license from the Department of Health. All animals underwent a general anesthetic. Vascular catheters were placed in the femoral artery and in the femoral vein. A Swan-Ganz Catheter was inserted for measurement of pulmonary artery pressure. Animals were randomized into three groups: Control, with measurements taken at baseline and half hourly up to 90 min; Endotoxin, receiving 5microg/Kg E. coli endotoxin intravenously after baseline measurements; and Endotoxin + Taurolidine, receiving 5g of taurolidine via intraperitoneal infusion 1 h before endotoxin administration. Main outcome measures were mean systemic arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), arterial oxygen tension (pO2), serum endotoxin concentration, and pulmonary myeloperoxidase. Endotoxin induced a significant lung injury characterized by an increase in pulmonary artery pressure, hypoxia, and systemic hypotension. Pretreatment with intraperitoneal taurolidine significantly attenuated these hemodynamic and respiratory changes. Serum endotoxin concentration was also significantly reduced as was lung myeloperoxidase. The data suggest that taurolidine may have a therapeutic role in preventing the lung injury seen in endotoxemia.     

Subcutaneous versus intravenous insulin therapy for glucose control in non‐diabetic trauma patients. A randomized controlled trial

What is known and Objective:  Hyperglycaemia in trauma patients admitted to the intensive care unit (ICU) is associated with increased morbidity and mortality. Our pilot study is a prospective randomized controlled trial comparing the impact of two glucose control regimens on outcomes in non‐diabetic trauma patients admitted with hyperglycaemia to the ICU. Methods:  Trauma patients with blood glucose levels (BGLs) ≥7·8 mm within the first 48 h of the hospital admission were randomized to receive intermittent SQ or continuous IV insulin to maintain BGLs between 4·4 and 6·1 mm. We excluded diabetics on the basis of history, or a glycosylated haemoglobin ≥6% on admission. We compared the effect of SQ vs. IV insulin therapy on the ICU length of stay (ILOS). Results and Discussion:  A total of 58 patients were included in the study. The SQ and IV groups were comparable in terms of age, gender, injury severity, revised trauma, Glasgow coma scores and type of trauma (blunt vs. penetrating). There was no significant difference between the two treatment groups in the ILOS (3 vs. 2 days, P = 0·084), hospital length of stay (8 vs. 6, P = 0·09), ventilator support days (6 vs. 3, P = 0·98), requirement for blood transfusion (P = 0·66), rates of infections (P = 0·70), acute kidney injury (P = 0·99) and mortality (P = 0·61). What is new and Conclusion:  There was no difference between SQ and IV insulin therapy in the ILOS in non‐diabetic trauma patients.     

Coronary flow reserve: measurement with transthoracic Doppler echocardiography is reproducible and comparable with positron emission tomography

Detection of early vascular changes indicated by lowered coronary flow reserve (CFR) would allow early treatment and prevention of atherosclerosis. The purpose of this study was to test whether it is possible to reproducibly measure CFR with transthoracic Doppler echocardiography (TTE) in healthy volunteers. We measured CFR using dipyridamole infusion in ten healthy male volunteers with two methods: TTE and positron emission tomography (PET) with oxygen‐15‐labelled water (group A). However, CFR was assessed twice with TTE in eight healthy male volunteers (group B) to study the reproducibility of this method. We compared CFRs obtained using TTE flow measurements in the left anterior descending coronary artery (LAD) and PET flow measurements in the corresponding myocardial area. Coronary flow in LAD could be measured in all subjects using TTE. By TTE, an average CFR based on peak diastolic flow velocity (PDV) was 2·72 ± 1·16, mean diastolic flow velocity (MDV) 2·56 ± 1·06 and velocity time integral (VTI) 1·87 ± 0·49. The results were reproducible in two repeated TTE studies (coefficient of variation in MDV 6·1 ± 4·3%, n=8). By PET, CFR was 2·52 ± 0·84. CFR assessed by TTE correlated closely with that measured by PET (MDV r=0·942, P<0·001; PDV r=0·912, P<0·002 and VTI r=0·888, P<0·006) and intraclass correlation was 0·929 (MDV) and tolerance limits for differences of CFRs was ?0·78 to 0·72. We show that CFR measured by TTE has an excellent correlation with CFR measured by PET. We also found that TTE measurements of CFR were highly reproducible.     

Pharmacokinetics and safety of bromotetrandrine (BrTet, W198) after single-dose intravenous administration in healthy Chinese volunteers

Objective: To investigate the safety and pharmacokinetics of bromotetrandrine (BrTet, W198), a novel inhibitor of P‐glycoprotein (P‐gp), after single‐dose i.v. infusion in healthy Chinese volunteers. Methods: We conducted a randomized, dose‐escalating, phase I clinical study for that purpose. Thirty healthy subjects received BrTet at the doses of 10, 20 or 30 mg/m² by i.v. infusion. Plasma and urine concentrations of bromotetrandrine were determined by using a liquid chromatography–tandem mass spectrometric (LC/MS/MS) method. AUC was calculated by the trapezoidal rule extrapolation method. C_max, T_max, t_1/2α, t_1/2β, Cl and V_d were compiled from the plasma concentration–time data. Results: Bromotetrandrine was generally well tolerated at all doses. No serious or severe adverse events were found in the study. The pharmacokinetic parameters of BrTet after single i.v. infusion doses of BrTet 10, 20 and 30 mg/m² were as follows: T_max were 1·5 h in three groups, C_max were 24·79, 39·59 and 64·31 μg/L, t_1/2α were 0·37, 0·29 and 0·30 h, t_1/2β were 62·88, 56·45 and 52·20 h. AUC_0–194h were 345·83, 688·15 and 1096·28 μg h/L, Cl were 23·68, 25·69 and 25·66 L h/m², V_d were 157·73,156·96 and 140·73 L/m². In urine, the total eliminate rate of originate compound was 0·61 ± 0·19%. Conclusions: This study suggested that bromotetrandrine was well tolerated in healthy volunteers within the dose range evaluated. The pharmacokinetics parameters of bromotetrandrine indicated that the compound was rapidly distributed and accumulated in the tissues, and slowly cleared from plasma, which supported the use of BrTet for a once or twice dosing per chemotherapy cycle.     

Comparison of micafungin and voriconazole in the treatment of invasive fungal infections in kidney transplant recipients

What is known and Objective: Invasive fungal infections are a major threat to renal transplant recipients. Micafungin and voriconazole are two useful antifungal agents for treating such infections. Our objective is to evaluate the comparative efficacy and safety of micafungin and voriconazole in the initial treatment of such infections. Methods: In this prospective, multicentre, open‐labelled, randomized, controlled trial, renal transplant recipients with invasive fungal infections were assigned to receive either micafungin or voriconazole. The enrolled subjects received a kidney transplant between March 2008 and March 2010 at one of the two transplant centres in Henan Province, China. The efficacy and adverse effects of the two treatments were compared. Results and Discussion: The clinical trial enrolled 65 patients, of whom 31 were treated with micafungin, and 34 with voriconazole. The rates of microbiological evidence of infection in the micafungin and voriconazole groups were 64·5% and 70·5%, respectively, whereas the rates of Candida as the major cultured fungus were 80·0% and 75·0%, respectively. Complicated bacterial infection rates in the two treatment groups were 38·7% and 32·4%, respectively, whereas complicated CMV viral infection occurred at a rate of 19·2% and 23·5%, respectively. Fungal infection within one to 3 months after transplant was 83·6% (26/31) and 85·3% (29/34) in the micafungin and voriconazole groups, respectively. There was no significant difference between the two groups in terms of efficacy, survival beyond 10 days and discontinuation of treatment because of lack of efficacy (P > 0·05). Mortality rates in the micafungin and voriconazole groups were 9·7% (3/31) and 12·1% (4/33), respectively. Rates of adverse effects in the two groups were 41·9% and 51·6% (P > 0·05), respectively. What is new and Conclusions: This is the first comparison of micafungin and voriconazole in renal transplant patients. Our study shows that the effectiveness of micafungin was similar to that of voriconazole in such patients.     

Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia

Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilatory failure and hypercapnia. On the other hand, it is known that acute metabolic acidosis can also negatively affect (respiratory) muscle function and, therefore, could lead to a deterioration of respiratory failure. Moreover, we reasoned that the impact of metabolic acidosis on respiratory muscle strength and respiratory muscle endurance could be more pronounced in COPD patients as compared to asthma patients and healthy subjects, due to already impaired respiratory muscle function. In this study, the effect of metabolic acidosis was studied on peripheral muscle strength, peripheral muscle endurance, airway resistance, and on arterial carbon dioxide tension (PaCO₂). Acute metabolic acidosis was induced by administration of ammonium chloride (NH₄Cl). The effect of metabolic acidosis was studied on inspiratory and expiratory muscle strength and on respiratory muscle endurance. Effects were studied in a randomized, placebo‐controlled cross‐over design in 15 healthy subjects (4 male; age 33·2 ± 11·5 years; FEV₁ 108·3 ± 16·2% predicted), 14 asthma patients (5 male; age 48·1 ± 16·1 years; FEV₁ 101·6 ± 15·3% predicted), and 15 moderate to severe COPD patients (9 male; age 62·8 ± 6·8 years; FEV₁ 50·0 ± 11·8% predicted). An acute metabolic acidemia of BE –3·1 mmol.L^?1 was induced. Acute metabolic acidemia did not significantly affect strength or endurance of respiratory and peripheral muscles, respectively. In all subjects airway resistance was significantly decreased after induction of metabolic acidemia (mean difference –0·1 kPa.sec.L^?1 [95%‐CI: ?0·1 –?0·02]. In COPD patients PaCO₂ was significantly lowered during metabolic acidemia (mean difference –1·73 mmHg [?3·0 –?0·08]. In healthy subjects and in asthma patients no such effect was found. Acute metabolic acidemia did not significantly decrease respiratory or peripheral muscle strength, respectively muscle endurance in nomal subjects, asthma, or COPD patients. Metabolic acidemia significantly decreased airway resistance in asthma and COPD patients, as well as in healthy subjects. Moreover, acute metabolic acidemia slightly improved blood gas values in COPD patients. The results suggest that stimulation of ventilation in respiratory failure, by induction of metabolic acidemia will not lead to deterioration of the respiratory failure.     

Effect of landiolol hydrochloride, an ultra-short-acting beta 1-selective blocker, on supraventricular tachycardia, atrial fibrillation and flutter after pulmonary resection

What is known and objective: Supraventricular tachycardia is a common complication after pulmonary resection. The objective of this study was to investigate the efficacy of landiolol hydrochloride, an ultra‐short‐acting β1‐blocker, in patients with post‐operative supraventricular tachycardia after pulmonary resection. Methods: The response to continuous intravenous infusion of landiolol was evaluated in 25 patients who developed post‐operative atrial fibrillation or atrial flutter after major pulmonary resection. Four patients had preoperative rate‐controlled chronic atrial fibrillation. The heart rate and blood pressure were compared before and after infusion of landiolol. Side effects and recurrence of supraventricular tachycardia after termination of landiolol infusion were also monitored. Results and discussion: The heart rate was reduced from 135 ± 24 bpm before landiolol infusion to a plateau rate of 85 ± 19 bpm during infusion (P < 0·0001). Heart rate reduction occurred in all but two patients. Conversion to normal sinus rhythm from supraventricular tachycardia occurred in 14 patients (56%). Recurrence of supraventricular tachycardia after stopping landiolol infusion was observed in 17 patients (68%), but all patients without preoperative AF were cured of post‐operative AF. There were no detectable side effects, including no adverse influence on the circulatory and respiratory systems. What is new and conclusion: Continuous intravenous infusion of landiolol was found to be effective and safe for supraventricular tachycardia after pulmonary resection.     

Evaluation of endothelium‐dependent vasodilation in the human peripheral circulation

Flow‐mediated vasodilation (FMD) in the brachial artery measured by ultrasound, and the increase in forearm blood flow (FBF) induced by local infusion of a muscarinic‐receptor agonist have both frequently been used to evaluate endothelium‐dependent vasodilation (EDV) in the human forearm. The present study intended to evaluate the relationship between these techniques and to investigate if vasodilation induced by the muscarinic receptor‐agonist methacholine (MCh) was owing to production of nitric oxide (NO). FMD during hyperaemia was assessed by ultrasound and FBF was measured by venous occlusion plethysmography during local infusion of MCh or L ‐arginine in the human forearm. Both these methods were applied in 26 individuals. In another 12 individuals forearm arterial and venous plasma concentrations of nitrate/nitrite (NOx) were measured together with FBF before and during local MCh infusion.While the change in brachial artery diameter induced by sublingually given nitroglycerine and the vasodilatory response to sodium nitroprusside (SNP) given locally in the forearm were significantly correlated (r=0·70, P<0·01), FMD showed no relationship with the vasodilation evoked by MCh (r=–0·03) or L ‐arginine (r=0·04). The five‐fold increase in FBF during MCh infusion was associated with a significant increase in venous plasma NOx concentrations (P<0·05) and a more than 11‐fold increase in forearm NOx‐release (P<0·01). Thus, a significant relationship between the two methods regarding the evaluation of endothelium‐independent vasodilation evoked by NO‐donors was found, but no relationship was found between the two methods regarding the evaluation of endothelium‐dependent vasodilation. Furthermore, vasodilation induced by MCh in the forearm seems to be induced by NO‐release.     

Digital X‐ray radiogrammetry: a new appendicular bone densitometric method with high precision

The precision of any given method for measurement of bone mineral density (BMD) is important in relation to the interpretation of repeated measurements over time, e.g. to monitor the course of suspected osteoporosis or follow the effect of therapy. In the present study a new bone densitometer using the digital X‐ray radiogrammetry (DXR) method (Pronosco X‐posure System?) is investigated with respect to its short‐term precision. The study was carried out on two groups of females, one consisting of 20 women between the ages of 30 and 40, and the other of 20 post‐menopausal women above the age of 64. The mean age of the premenopausal women was 35·2 years and the mean DXR BMD was 0·578 g cm^?2. The mean age of the post‐menopausal women was 68·2 years and the mean DXR BMD was 0·489 g cm^?2. The short‐term precision of the two groups was evaluated using the coefficient of variation (CV%) and corresponding 90% confidence intervals. The coefficient of variation in the premenopausal group was 0·68% with a 90% confidence interval of 0·57%?0·83%. The coefficient of variation in the postmenopausal group was 0·61% with a 90% confidence interval of 0·52–0·75%. It can be concluded from the present study that the short‐term in vivo precision error of the DXR method is low in both pre‐ and post‐menopausal women. When the results of the study are compared to data reported in the literature, the performance of the DXR method seems to be at least equivalent with peripheral DXA.