Drug-associated renal dysfunction

Acute renal failure (ARF) in patients in the ICU is associated with a high mortality. Drug-induced renal dysfunction is an important, yet often overlooked, cause of ARF in this patient population. A drug use evaluation at the authors' institution, to assess the prescribing patterns of potential nephrotoxins in the adult and pediatric ICUs, found that antibiotics (aminoglycosides, amphotericin B, penicillins, cephalosporins, acyclovir), nonsteroidal anti-inflammatory drugs, contrast dye, and various other nephrotoxic medications are used widely in all of the ICUs. By focusing on several commonly prescribed classes of nephrotoxic medications in the ICU, this article reviews the general mechanisms of drug-associated renal dysfunction.     

Drug-associated pulmonary arterial hypertension

Introduction: While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into “definite”, “likely”, “possible”, or “unlikely” to cause pulmonary arterial hypertension, based on the strength of evidence.

Objective: This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension.

Methods: A systematic search was conducted using PubMed covering the period September 1970– 2017. The search term utilized was “drug induced pulmonary hypertension”. This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism.

Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension.

Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection.

Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear.

Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension.

Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents; nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports.

Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension.

Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes.

Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects.

Conclusions: Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an individual to PAH have yet to be elucidated.     

Drug-associated disease: hematologic dysfunction

Hematologic dysfunction, including thrombocytopenia, anemia, neutropenia, thromboses, and coagulopathy, occur commonly during critical illnesses. A major challenge is to identify drug-induced causes of hematologic dysfunction. Given the wide variety of drug-induced hematologic effects, clinicians always should consider any concomitant drugs in the differential diagnosis of acquired hematologic dysfunction. The most severe effects include drug-induced aplastic anemia, heparin-induced thrombocytopenia, and drug-induced thrombotic microangiopathy. Certain drugs are associated with multiple hematologic effects. For example, cisplatin can cause hemolytic uremia syndrome and erythropoietin deficiency, and quinine can precipitate immune-mediated thrombocytopenia, immune-mediated thrombocytopenia, and thrombotic microangiopathy.     

Treatment of heat stroke

Immediate cooling and support of organ-system function are the two main therapeutic objectives in patients with heat stroke. When cooling is rapidly initiated and both the body temperature and cognitive function return to the normal range within an hour of onset of symptoms, most patients recover fully. Immersion in an ice-water bath is the most effective cooling method, and evaporative cooling is a rapid and effective alternative. To prevent the development of rhabdomyolysis-induced acute renal failure, aggressive IV rehydration should be continued for first 24 to 72 hours with the goal of maintaining a minimum urine output of 2 mL/kg/h. Treatment of heat cramps also consists of fluid and salt replacement (PO or IV) and rest in a cool environment. In severe cases, IV magnesium sulphate may be effective to relieve muscle cramping.     

Sports and heat stroke

We described Characteristic of the heat stroke in the sports activity in Japan. It was common in teenage men, and 15 years old had a peak with a man, the woman. Most patients did not need specific treatment. Many happened from the end of July on the outdoors around 3:00 p.m. in mid-August. There are many in order of baseball, football, tennis, and a basketball. Running and cycling had high severity of illness. Probably, grasp of an environmental condition, suitable sportswear, suitable hydration, and condition management are the best things as preventive measures.     

药物相关性脊髓蛛网膜炎6例报道

目的 探讨药物相关性脊髓蛛网膜炎的临床特点.方法 对经治的6例药物相关性脊髓蛛网膜炎患者进行回顾性分析.结果 患者均急性起病,临床以双下肢麻木、乏力、二便障碍为主要表现,脑脊液常规表现蛋白升高明显,白细胞正常或轻度升高.结论 药物相关性脊髓蛛网膜炎一旦发生,对各种药物治疗均不敏感,预后差.在临床工作中应尽量预防其发生.     

Drug-associated disease: cytochrome P450 interactions

Critically ill patients generally are older, frequently have organ failure, and commonly receive multiple medications, all of which make them susceptible to adverse effects of drugs. Drug interactions are a common adverse effect, and many are predictable based on understanding the mechanisms that underlie drug interactions. This article identifies commonly used medications in critically ill patients and the associated drug interactions that may occur with emphasis on the cytochrome P450 enzyme system.     

The value of the exertional heat stroke score for the prognosis of patients with exertional heat stroke

ObjectiveThis study aims to evaluate the exertional heat stroke score (EHSS) system for the prognosis of exertional heat stroke (EHS) patients.MethodsForty-two EHS patients who had been treated in our hospital between January 2017 and December 2019 were divided into two groups according to their prognosis, a survival group and a non-survival group. All the patients had received comprehensive EHS treatment after admission, and their EHSS parameters were collected within 24 h of admission, including body temperature, hepatorenal function, and coagulation function. A retrospective comparative evaluation was made of the effectiveness of the EHSS, the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) in making an EHS prognosis.ResultsAmong 42 patients, 28 patients were treated successfully and discharged from the hospital, 5 were given a poor prognosis, and 9 died, amounting to a fatality rate of 21.42%. Univariate analysis showed that within 24 h of admission, the differences were statistically significant (p < 0.05) in the comparison of the following factors: lactate concentration, platelets, prothrombin time, fibrinogen, troponin, aspartate aminotransferase, total bilirubin, urinary creatinine, acute gastrointestinal injury, temperature, and Glasgow coma score. However, no statistically significant difference in blood pH was observed between the two groups of patients (p = 0.117). The EHSS, APACHE II, and SOFA scores of the survival group were significantly lower than those of the non-survival group (p < 0.001). The area under the receiver operating characteristic curve of the EHSS, APACHE II and SOFA scores were the area under the curve (AUC) _EHSS = 0.96 (0.901, 0.990), AUC _{Apache II} = 0.895 (0.802, 0.950), and AUC _SOFA = 0.884 (0.837, 0.964), respectively. Thus, the EHSS diagnostic efficacy of the survival group was significantly higher than that of the other two scores. In addition, the sensitivity and specificity of EHSS were higher than those of the APACHE II and SOFA scores.ConclusionThe EHSS has a good diagnostic efficacy for the prognosis of EHS patients and is significantly higher than that of the APACHE II and SOFA scores. This finding provides a theoretical basis for further increasing the rescue success rate of EHS patients and improving their prognostic quality of life.     

Severe heat stroke with multiple organ dysfunction

In a case report recently published in Critical Care, Broessner and coworkers [1] claim to have successfully treated a patient with heat stroke by using a specific cooling device. We should like to raise some important issues.     

热射病与实验室检查的相关分析

目的 探讨实验室相关检查对预防热射病并发症的重要性.方法 对35例确诊为热射病患者首次实验室检查结果进行相关分析.结果 相关实验室检查异常结果均达到60%以上.结论 实验室检查对早期发现热射病并发症有重要意义,对其并发症采取相应的治疗措施,可降低患者的死亡率和致残率.     

Heat stroke and related heat stress disorders

Medical disorders related to environmental heat exposure are exceptionally common in persons who perform hard work in hot climates. They are also common in competitive athletes as well as in persons who participate in casual exercise to maintain health. The important issue of salt and water disturbances consequent to heavy sweating in hot climates is discussed in detail as are mechanisms of potassium deficiency and its implications. The major forms of environmental heat illness including heat syncope, heat cramp, heat exhaustion, and heat stroke are presented in detail with relevant clinical examples. A discussion of the differential diagnosis of hyperthermia and rhabdomyolysis follows. Because of the difference in treatment and complications, heat stroke is subdivided into the classic variety that affects the elderly and very young and that form that follows heavy physical work and is always associated with rhabdomyolysis. Because severe heat exhaustion and heat stroke are life-threatening disorders, the chapter includes a detailed discussion of complications and plans for treatment.     

热射病患者的脑部MRI表现

目的：探讨热射病患者的脑部MRI表现。材料与方法选取8例经临床诊断为热射病的患者,均于发病后2～5d内行颅脑磁共振检查,检查序列包括T1WI、T2WI、T2-FLAIR、DWI、SWI;其中5例患者并进行了2～4次的随访MRI检查。结果8例热射病患者中5例可检出异常信号,部位包括脑干、小脑齿状核、小脑脚、小脑半球、海马、放射冠、半卵圆中心及右额颞顶叶,病灶性质包括微出血、细胞毒性水肿、血管源性水肿、出血性梗死、脑炎,小脑病变呈对称性分布。结论热射病可引发脑组织缺血、出血、梗死、炎症等多种性质病变,MRI表现具有一定特征性,常出现小脑的异常且呈对称性分布。     

Is dantrolene effective in heat stroke patients?

Dantrolene (2.45 mg/kg body weight, range 2 to 4) was administered iv in eight heat stroke (HS) patients and compared with a control group of 12 patients of similar age, weight, and temperature range (41.9 degrees to 44 degrees C). Body surface cooling was conducted in air conditioned rooms at temperatures of 18 degrees to 23 degrees C. Mean cooling time in the dantrolene group was 49.7 +/- 4.4 (SEM) min, whereas cooling time in the control group was 69.2 +/- 4.8 min. The decrease in temperature was significantly greater in the dantrolene group, for whom the cooling time was decreased by about 19.5 min (p less than .01). Although cooling time was significantly shorter in the dantrolene group, there was no difference in the recovery of both groups. Dantrolene is an expensive drug and justification for its routine use in HS remains to be evaluated.     

The Japanese government's efforts to prevent heat stroke

In recent years, as one of the effects of global warming and heat island phenomenon, the risk of heat stroke in daily life is increasing. The worst heat wave in our history attacked in 2010, which killed more than 1,700 people. Therefore, the Japanese Government, including the Ministry of the Environment, has promoted the following measures: (1) Provision of information about prediction and observation of temperature and warning of hot weather (2) Awareness-raising of preventive measures appropriate to the heat stroke (3) Dissemination of information on the occurrence of heat stroke, e.g. the number of deaths, the number of persons taken to hospital by ambulance (4) Promotion of research and study on heat stroke     

抗精神病药物所致热射病一例

正患者女,36岁。7年前无明显诱因出现口干、多饮,每天饮水量约4000 ml,多尿,尿量与饮水量相当,18 d前患者出现发热,伴乏力,就诊于牟平中医院,诊断为"尿路感染",治疗3 d患者体温恢复正常,但病情未愈,自行出院;7 d前患者出现反应迟钝,伴纳差;病情进行性加重,5 d前又开始发热,当时体温38℃,伴神志恍惚,伴大小便失禁,于牟平中医院住院治疗,诊断为"2型糖尿病、肺炎、胆囊泥沙样结石、精神分