Urodilatin: a new approach for the treatment of therapy-resistant acute renal failure after liver transplantation

Abstract A pilot study was performed in patients after liver transplantation (Ltx) to examine the effect of continuous intravenous urodilatin (URO, CDD/ANP-95–126)-infusion as an alternative therapy of acute renal failure (ARF) resistant to conventional therapy. Eight patients who developed ARF after liver transplantation and fulfilled requirements for haemo-dialysis/haemofiltration were treated. After URO infusion was started, renal function improved and all patients developed a strong diuresis and natriuresis within 2–4h. The extracellular expansion due to sodium and water retention in anuric/oliguric ARF lead to an increased central venous pressure (CVP) and elevated blood pressure. During the URO infusion CVP declined and systolic, as well as diastolic, blood pressure were stable. In six patients where haemodialysis/haemofiltration could be avoided, serum creatinine (SC) and blood urea nitrogen (BUN) declined during URO treatment and creatinine clearance (CC) also improved significantly. Fluid and electrolyte disturbances changed promptly and normalized. This was in concordance with renal excretion of electrolytes. Two patients still required haemodialysis/haemofiltration. The six patients who did not require haemodialysis/haemofiltration after URO treatment normalized concerning their renal function and did well in a control period of 12 weeks. The study shows that continuous low dose URO infusion may present a new concept for treatment of postoperative acute renal failure resistant to conventional therapy.     

Comparison of the Cardiovascular Toxicity of Three Tricyclic Antidepressent Drugs: Imipramine,Amitriptyline, and Doxepin

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition continuous clacium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of sever hypercalcemia and hyperglaycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.     

Acute hemodynamic effects of intravenous amiodarone treatment in paediatric cardiac surgical patients

Introduction  The haemodynamic response after an IV-loading dose of amiodarone followed by continuous infusion for various supraventricular and ventricular tachycardias was studied in children immediately after corrective surgery for congenital heart defects. Methods  Observational study over a 10-year period. Seventy-one out of 2651 patients (2,885 procedures, 2,106 bypass procedures) received amiodarone therapy for newly detected postoperative tachyarrhythmias. All patients received catecholamine infusions as standard post-op therapy to support cardiac function and output. In most cases a loading dose of amiodarone was given over 1–4 h followed by a continuous infusion. Catecholamine infusion dose requirements were monitored as was heart rate, blood pressure, central venous pressure, and sedation dose requirements pre treatment and at 0.5, 1, 2, 4, 8, 12 and 24 h after the begin of the amiodarone administration. Results  After 1 h there was a significant decrease of heart rate from 194.5 bpm (±31.9) to 157.5 bpm (±34.3) and an increase of the mean arterial blood pressure from 52.8 (±11.4) to 56.0 (±9.8) mmHg, with a subsequent decrease of filling pressures. The catecholamine dose required could be decreased as could the dose for sedation. Rate control was achieved at 277.4 min (±344) and rhythm control at 685.8 min (±988.5) respectively. Based on a preliminary interim analysis a specific treatment protocol was established and used in 32 patients. Conclusion  A slow bolus administration of 5 mg/kg amiodarone over at least 60 min followed by one or two additional boluses or a continuous infusion with 10–20 mg/kg day⁻¹ is a safe treatment strategy without the need for additional inotropic support and with dramatic improvement of heart rate, blood pressure and filling pressures. This protocol can be recommended for paediatric patients in the early postoperative setting.     

Effect of mode of hydrocortisone administration on glycemic control in patients with septic shock: a prospective randomized trial

Introduction  

Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock. The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered. Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach.     

高分子材料聚砜膜滤器应用于老年急性重症胰腺炎47例

目的:探讨聚砜膜滤器连续血液净化治疗急性重症胰腺炎时降低胰淀粉酶及各种炎性递质的作用.方法:对47例老年急性重症胰腺炎患者实施聚砜膜滤器连续血液净化治疗,于治疗前,治疗12,24 h及治疗后对患者进行血生化指标,淀粉酶、血常规、C-反应蛋白、血气分析检测.同时记录患者心率,平均动脉压,中心静脉压,呼吸频率和体温等,进行APACHE Ⅱ,SAPS Ⅱ和合并多脏器功能障碍综合征评分.结果:治疗后患者APACHE Ⅱ,SAPS Ⅱ,合并多脏器功能障碍综合征评分明显降低,血肌酐、血淀粉酶、C-反应蛋白均明显低于治疗前.治疗后反映肺功能的氧指数有明显改善,心率减慢,中心静脉压下降,平均动脉压下降,反映心功能状态的压力调整心率,治疗12,24 h较治疗前降低.治疗过程中HCO_3~-较治疗前升高,血Ca~(2+),Mg~(2+)较治疗前也有所升高.连续性血液净化治疗对维持血Ca~(2+),Mg~(2+)在正常值范围作用尤为显著,但在停止治疗后,血清Ca~(2+),Mg~(2+)有所降低.结论:采用聚砜膜滤器连续血液净化治疗后,心、肺功能的改善与组织器官的间质水肿减轻有关;就清除各种炎性递质、淀粉酶而言,治疗时间越长越好.聚砜膜滤器连续血液净化治疗老年急性重症胰腺炎效果是肯定的.     

Combined therapy in the treatment of hypertension

The majority of patients with hypertension need at least two antihypertensive agents to achieve blood pressure (BP) objectives. As current European guidelines for the treatment of arterial hypertension recommend, combined therapy is required when monotherapy fails and as a first-line treatment in certain situations, such as subjects at high or very high cardiovascular risk, markedly elevated BP values, or when lower targets are required (<130/80 mmHg). The advantages of combined therapy are well known and include an earlier and higher antihypertensive efficacy because of complementary mechanisms of action, and a lower incidence of side effects due to the possible compensatory responses and, in many cases, the lower doses used. In the present study, available evidence about the efficacy and tolerability of combined therapy for the treatment of hypertension is updated.     

Basal-rate intravenous insulin infusion compared to conventional insulin treatment in patients with type II diabetes. A prospective crossover trial

We compared continuous basal-rate intravenous insulin infusion, delivered by means of a totally implantable pump, to two types of conventional insulin administration in patients with type II (non-insulin-dependent) diabetes in a prospective crossover trial. Ten patients entered the study, and 5 completed all three 8-mo study periods. When results from the infusion study period were compared with results from the period involving single daily injections of ultralente insulin, significant improvements were noted in the pump arm in glycosylated hemoglobin concentrations (which were nearly normal), M-component values, mean daily outpatient fasting blood glucose concentrations, mean fasting and 24-h blood glucose concentrations during an inpatient 24-h glycemic profile, and urinary glucose concentrations. When the pump arm was compared to a period of single daily injections of lente insulin, three of six monthly mean fasting blood glucose concentrations and overall means for the entire study period were significantly lower during the pump arm than during the lente arm; in addition, significantly fewer hypoglycemic reactions were noted during infusion therapy than during lente therapy. Finally, mealtime free-insulin and C-peptide excursions appeared to be greater during infusion treatment when compared with lente or ultralente treatment. In the 50% of patients who completed the study, it appeared that significant improvements in glycemic control could be achieved by simple basal-rate intravenous insulin infusion compared with conventional treatment with single daily injections of ultralente or lente insulin without an increased incidence of symptomatic hypoglycemia.     

Carboxyhemoglobin measurement by hospitals: implications for the diagnosis of carbon monoxide poisoning

Most case definitions for carbon monoxide (CO) poisoning include demonstration of an elevated blood carboxyhemoglobin (COHb) concentration. Further, it is generally believed that treatment of CO poisoning is more effective when performed as soon as possible after the exposure. This suggests that a hospital's inability to measure blood COHb could lead to delayed or missed diagnosis or treatment. This study evaluated the ability of hospitals in the Pacific Northwest to measure COHb levels. The clinical laboratory of every acute care hospital in Washington, Idaho, Montana, and Alaska was surveyed regarding the ability to measure COHb levels, the method utilized and the time required. If they could not measure COHb, they were asked whether samples are sent elsewhere, the location of the referral laboratory, and time required. Results were then compared to the list of hospitals referring CO-poisoned patients to a regional center for hyperbaric oxygen therapy from 2003-2004. In the four states, only 44% of acute care hospitals have the capability to measure COHb. The remaining 56% send blood samples to other laboratories. The average time to get a result is 10 +/- 10 min in hospitals with co-oximetry and 904 +/- 1360 min in those without, a difference of 15 h (p < 0.0001). When samples are sent out, the average distance is 121 miles, often bypassing a hospital with CO-oximetry capability. Over 90% of CO-poisoned patients referred for hyperbaric treatment came from hospitals able to measure COHb. Fewer than one-half of acute care hospitals in a four-state region have the capability to measure COHb levels. This has the potential to significantly impact diagnosis or treatment of patients with acute CO poisoning.     

Continuous hemofiltration/hemodiafiltration in critical care.

Continuous hemofiltration and continuous hemodiafiltration (CHF/CHDF) were developed as continuous renal replacement therapy for patients with severe conditons and has come to be widely performed mainly in critical care, taking the place of intermittent hemodialysis. The membrane pore size of a hemofilter used for CHF/CHDF allows passage of substances ranging from 30,000 to 50,000 Da, and the method for solute removal in CHF/CHDF employs the principle of convection, which is advantageous for removing middle- to high-molecular-weight substances. As apheresis therapy to remove pathogenic substances in blood, CHF/CHDF is therefore being investigated for its possible effect on various morbid conditions. It has recently been found that CHF/CHDF removes humoral mediators including cytokines, particularly in severe systemic inflammatory response syndromes such as septic shock and severe acute pancreatitis. CHF/CHDF is thus beginning to be performed for the prevention and treatment of organ dysfunction secondary to septic shock, trauma, or acute pancreatitis. CHF/CHDF is also efficacious as artificial liver support in preventing adverse effects caused by plasma exchange (PE) and for continuous removal of hepatic coma-inducing substances. CHF/CHDF is effective for various morbid conditions not only as renal replacement therapy, but also as apheresis therapy and is expected to be applied more widely in critical care in the future.     

Efficacy and limitation of apheresis therapy in critical care.

Apheresis therapy such as plasma exchange and plasma adsorption has become therapeutic tools in critical care. The indications for apheresis therapy in ICU patients include fulminant hepatic failure, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), autoimmune disease, and sepsis. During the past 11 years, 150 patients with various kinds of critical illnesses were treated with apheresis therapy in our ICU, and the overall survival rate was 50%. Apheresis therapy is especially useful in the treatment of a patient with fulminant hepatic failure because liver transplantation is seldom performed in Japan; therefore, the patient should be treated with artificial liver support. When plasma exchange is performed on the critically ill, continuous hemodiafiltration should be performed simultaneously to overcome the adverse effects of plasma exchange such as hypernatremia, metabolic alkalosis, and abrupt changes in colloid osmotic pressure and to enhance the removal rate of the causative middle molecular weight substances of hepatic failure or hepatic coma.     

Hypoxic respiratory failure in term newborns: clinical indicators for inhaled nitric oxide and extracorporeal membrane oxygenation therapy

PURPOSE: The criteria for starting extracorporeal membrane oxygenation (ECMO) therapy in term newborn patients with hypoxemic respiratory failure consist of an oxygenation index (OI) of 25 or higher and alveolar-arterial oxygen (Aao(2)) gradient of more than 600 at sea level. In such conditions, inhaled nitric oxide (iNO) may improve oxygenation and reduce the need for ECMO therapy. We studied early changes in OI and Aao(2) gradients in response to iNO treatment that may indicate a need to continue iNO treatment or the necessity to start an ECMO therapy. MATERIALS AND METHODS: In this prospective study, we used 34 outborn neonatal patients that were referred to our pediatric critical care unit in a children's hospital for ECMO therapy with diagnosis of hypoxemic respiratory failure. In all patients, iNO therapy, starting at 80 ppm, was instituted either during transport or on arrival to hospital. Response to iNO was assessed after 1 hour, at which time, iNO concentration was reduced to 40 ppm, provided there was more than 20% improvement in either or both oxygenation indices. Patients who did not respond positively to continuous iNO therapy and met ECMO criteria were given ECMO therapy. RESULTS: Inhaled nitric oxide therapy alone was successful in 10 (29%) of 34 patients. Eighteen patients (53%) required ECMO therapy within the first 10 hours of iNO treatment (early ECMO therapy), whereas 6 other neonates (18%) became eligible for ECMO therapy after prolonged (2-4 days) iNO treatment (late ECMO therapy). No mortality occurred with any treatment. Within 4 hours after iNO therapy, patients who required early ECMO therapy had significantly higher OI and Aao(2) gradients than patients who were treated with iNO therapy alone (P<.01, analysis of variance followed by Tukey-Kramer multiple comparison test). Six of 34 patients (18%), categorized as late ECMO therapy, on the average, had initially higher levels of OI and mean airway pressure than neonates in iNO treatment and early ECMO therapy. CONCLUSION: Persisting levels of OI of more than 20 or Aao(2) gradients of more than 600 after 4 hours of iNO therapy could be indicative of an immediate need for ECMO therapy.     

Kontinuierliche subkutane Buprenorphinapplikation in der Therapie karzinombedingter Schmerzen

Introduction Buprenorphine is well known in cancer pain therapy because of the long duration of its action and high analgesic potency. Many studies exist about the intravenous and sublingual application form; however, few data are available on its use by the continuous subcutaneous route. Methods Twenty-five patients were analysed retrospectively over 956 days who has been treated with continuous subcutaneous buprenorphine for cancer-related pain. In 7 of these 25 patients plasma analyses were performed. Due to a modified sensitive HPLC method with electrochemical detection for the analysis of buprenorphine in plasma, a detection limit of 40 pg/ml could be obtained. The other analytical methods for plasma concentration have detection limits between 150 and 500 pg/ml. Results During the treatment with continuous subcutaneous buprenorphine it was necessary to increase the initial average daily dose of 1.07 (+/-0.41) mg to 1.58 (+/-0.58) mg. The initially high pain intensity (rated from 0 to 100%) of 67% could be reduced to a moderate pain of 26% on average. Only 2 patients had to be switched over to morphine because of insufficient analgesia. In no case did complications occur that required intervention or would have made it necessary to change the pain therapy. Eighty percent of the patients judged this kind of treatment as effective and comfortable. Most often patients complained about drowsiness, low appetite and constipation. Because of the progress of the cancer disease these effects could not clearly be related to treatment side effects. With 7 of 25 patients the median daily dose of 1.2 (minimum 0.9-maximum 2.3) mg buprenorphine was related to the median plasma concentration of 438 (minimum 64-maximum 3374) pg/ml. In one case with progressive liver dysfunction, the potential risk of cumulation with buprenorphine could be controlled with this method. Conclusions Continuous subcutaneous buprenorphine with external infusors is a safe and efficient cancer pain therapy without severe side effects. Because of its ceiling effect, it is not as effective as morphine, but can be discussed as an alternative if other opioids cause incompatibility reactions.     

Encapsulation of FITC to monitor extracellular pH: a step towards the development of red blood cells as circulating blood analyte biosensors

A need exists for a long-term, minimally-invasive system to monitor blood analytes. For certain analytes, such as glucose in the case of diabetics, a continuous system would help reduce complications. Current methods suffer significant drawbacks, such as low patient compliance for the finger stick test or short lifetime (i.e., 3-7 days) and required calibrations for continuous glucose monitors. Red blood cells (RBCs) are potential biocompatible carriers of sensing assays for long-term monitoring. We demonstrate that RBCs can be loaded with an analyte-sensitive fluorescent dye. In the current study, FITC, a pH-sensitive fluorescent dye, is encapsulated within resealed red cell ghosts. Intracellular FITC reports on extracellular pH: fluorescence intensity increases as extracellular pH increases because the RBC rapidly equilibrates to the pH of the external environment through the chloride-bicarbonate exchanger. The resealed ghost sensors exhibit an excellent ability to reversibly track pH over the physiological pH range with a resolution down to 0.014 pH unit. Dye loading efficiency varies from 30% to 80%. Although complete loading is ideal, it is not necessary, as the fluorescence signal is an integration of all resealed ghosts within the excitation volume. The resealed ghosts could serve as a long-term (>1 to 2 months), continuous, circulating biosensor for the management of diseases, such as diabetes.     

Management of ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease. The disease is diagnosed on the basis of clinical parameters and endoscopic-histologic evaluation. 5-aminosalicylic acid (5-ASA, mesalamine) represents the first-line treatment of choice. For patients with distal and left-sided disease the use of rectal preparations is effective. Most patients respond to 5-ASA suppositories or to topic steroids such as budesonide suppositories or hydrocortisone foam. For patients with extended disease, oral medications are mandatory. In case of low- to moderate-grade inflammation, 5-ASA preparations should be implemented. In the case of severe disease treatment with steroids is required. Following induction of remission, prophylactic treatment with 5-ASA (1.5 g/d) should be maintained. For patients with frequent or severe relapses, immunosuppressive therapy with azathioprine or 6-mercaptopurine is indicated. In case of a fulminant course of disease, treatment with intravenous cyclosporine is required in patients who have not responded to high-dose intravenous steroids. When all conservative treatment options fail, proctocolectomy with construction of an ileoanal pouch should be performed. New therapeutic strategies such as infliximab and interferons are being evaluated in clinical trials. The long-term complications of ulcerative colitis include steroid-induced osteoporosis and anemia and should be treated adequately. Finally, the risk for development of colorectal cancer increases steadily with disease duration and dysplasia should be screened for by endoscopic surveillance programs.     

甲基强的松龙联合环磷酰胺冲击治疗难治性肾病对心功能的影响与护理

目的 探讨甲基强的松龙(MP)联合环磷酰胺(CTX)冲击治疗难治性肾病对患儿心功能的影响.方法 对收治的30例难治性肾病患儿,在进行MP联合CTX冲击治疗时,监测患儿的心功能,记录治疗前、治疗中患儿的心率、血压变化,并观察并发症情况.结果 治疗中患儿的心率加快,血压升高,与治疗前比较有统计学意义(P＜0.05).MP治疗时心悸、头晕等并发症易发生在第3次治疗中;CTX治疗时恶心、呕吐、心悸等并发症易发生在首次疗程中,骨髓抑制、肝功损害易发生在后续疗程中.结论 在MP联合CTX冲击治疗难治性肾病时,应监测患儿的心功能变化,根据心率、血压变化及时采取相应的措施,减少并发症的发生.     

Barriers to blood pressure control in African Americans. Overcoming obstacles is challenging,but target goals can be attained

Outdated and biased attitudes and care standards impede optimal care of hypertension in African Americans. The negative expectations that blood pressure targets cannot be reached must be overcome by systematic and appropriate education and treatment. However, physicians should expect that (1) African American patients with elevated blood pressure benefit from early and intensive management, (2) blood pressure can be maintained at goal with appropriate therapeutic lifestyle changes and medications, and (3) complications related to high blood pressure can be avoided. To bring blood pressure down to the target goal, combination pharmacologic therapy is often required. When extensive efforts to achieve blood pressure control prove unattainable in the primary care setting, consultation with a hypertension specialist should be considered.     

动脉导管未闭封堵术后重度溶血的外科治疗一例

机械性溶血是介入治疗置入封堵器的严重并发症之一,其主要原因是人体血流与粗糙的封堵器表面发生摩擦导致红细胞破裂,可表现为酱油色样尿,伴血红蛋白降低、黄疸等症状,可予降压、补液、糖皮质激素等保守治疗。保守治疗无效时,需及时再次行封堵术或外科手术治疗。该文报道1例动脉导管未闭封堵术后出现重度溶血的46岁女性患者,经保守治疗无效,予创新性手术方式治疗后,症状好转出院。结合相关文献对病例资料进行分析总结,阐述了先天性心脏病封堵术后的并发症及处理方法。该文介绍的手术方式可缩短手术时间及降低操作复杂程度,希望能为广大同行提供一丝灵感或经验。     

Management of refractory hypertension

True refractory hypertension is unusual in clinical practice, thanks to the widespread availability of antihypertensive drugs and national mandate to optimize blood pressure control levels in the community. However, at times the blood pressure may become refractory to initial drug therapy. When the blood pressure levels do not reach a target level despite usual therapy, hypertension is considered refractory. There should be proper evaluation of such patients to determine the factor(s) responsible for resistance to therapy. In many patients, proper adjustment of drug doses, including effective use of diuretics, restores the blood pressure level. For some patients, potent drug therapy, such as hydralazine or minoxidil, must be considered. Based upon clinical course, work-up for secondary causes of hypertension should be considered in selected patients. Refractory hypertension requires proper analysis of etiologic factors and consideration of rational drug selection, and at times, work-up for secondary causes of hypertension.     

Continuous positive airway pressure for obstructive sleep apnea in children

QuestionA 12-year-old child underwent adenotonsillectomy for treatment of obstructive sleep apnea (OSA) but continues to snore at night and struggles with attentiveness at school. The child’s parent uses a continuous positive airway pressure (CPAP) machine at night and wonders whether the same therapy could be used in children.AnswerUnlike in adults, pediatric OSA is commonly related to adenotonsillar hypertrophy and is often amenable to treatment with adenotonsillectomy. As an alternative to surgery or in cases of postsurgical persistence of OSA, CPAP has shown effectiveness in improving both polysomnographic parameters and daytime neurobehavioural symptoms in children with OSA. Adherence to CPAP therapy is a challenge in children and requires parental education and special considerations such as a mask acclimatization period.