Rational treatment of acid-base disorders

Acid-base derangements are encountered frequently in clinical practice and many have life-threatening implications. Treatment is dependent on correctly identifying the acid-base disorder and, whenever possible, repairing the underlying causal process. Bicarbonate is the agent of choice for the treatment of acute metabolic acidosis. Controversy surrounds the use of alkali therapy in lactic acidosis and diabetic ketoacidosis, but bicarbonate should clearly be administered for severe acidosis. In most patients with mild to moderate chloride-responsive metabolic alkalosis, providing an adequate amount of a chloride salt will restore acid-base balance to normal over a matter of days. In contrast, therapy of the chloride-resistant metabolic alkalosis is best directed at the underlying disease. When alkalemia is severe, administering hydrochloric acid or a hydrochloric acid precursor may be necessary. Treatment of respiratory acidosis should be targeted at restoring ventilation; alkali should be administered only for superimposed metabolic acidosis. The therapy of respiratory alkalosis is centred on reversal of the root cause; short of this goal, there is no effective treatment of primary hypocapnia. The coexistence of more than one acid-base disorder (i.e. a mixed disorder) is not uncommon. When plasma bicarbonate concentration and arterial carbon dioxide tension (paCO2) are altered in opposite directions, extreme shifts in pH may occur. In such cases, it is imperative that the nature of the disturbance is identified early and therapy directed at both disorders.     

盐酸精氨酸治疗脑外伤严重代谢性碱中毒30例分析

目的分析盐酸精氨酸持续微量泵输入治疗脑外伤患者严重代谢性碱中毒的量效关系及对近期患者预后的影响。方法选择成年严重颅脑外伤合并严重碱中毒患者30例,持续微量泵输注盐酸精氨酸0.55 g/（h.kg）,通过血气分析观察治疗前后碱剩余（BE）变化情况,计算精氨酸治疗碱中毒的量效关系。结果盐酸精氨酸治疗严重代谢性碱中毒后,BE下降（11.94±3.45,8.74±3.67,P〈0.001）,pH（7.47±0.06,7.45±0.05,P〈0.05）,PaCO2也同时有下降（49.73±10.48,46.53±9.26,P〈0.05）,Na^＋、Cl^-和K^＋变化不明显;BE下降梯度为△3.19±2.24。结论盐酸精氨酸持续微量泵输入可以有效纠正脑外伤患者严重碱中毒。     

Amino Acid requirements in critically ill patients with acute kidney injury treated with continuous renal replacement therapy

Acute kidney injury in critically ill patients is often a complication of an underlying condition such as organ failure, sepsis, or drug therapy. In these patients, stress-induced hypercatabolism results in loss of body cell mass. Unless nutrition support is provided, malnutrition and negative nitrogen balance may ensue. Because of metabolic, fluid, and electrolyte abnormalities, optimization of nutrition to patients with acute kidney injury presents a challenge to the clinician. In patients treated with conventional intermittent hemodialysis, achieving adequate amino acid intake can be limited by azotemia and fluid restriction. With the use of continuous renal replacement therapy (CRRT), however, better control of azotemia and liberalization of fluid intake allow amino acid intake to be maximized to support the patient's metabolic needs. High amino acid doses up to 2.5 g/kg/day in patients treated with CRRT improved nitrogen balance. However, to our knowledge, no studies have correlated increased amino acid intake with improved outcomes in critically ill patients with acute kidney injury. Data from large, prospective, randomized, controlled trials are needed to optimize the dosing of amino acids in critically ill patients with acute kidney injury who are treated with CRRT and to study the safety of high doses and their effects on patient morbidity and survival.     

Hypokalemic, metabolic alkalosis induced by high-dose ampicillin sodium.

A case of hypokalemic metabolic alkalosis precipitated by high-dose intravenous ampicillin sodium is discussed. Cases of hypokalemic metabolic alkalosis attributable to ampicillin sodium have not been reported previously. There have been reports of this phenomenon associated with high doses of penicillin sodium and carbenicillin disodium. The possible mechanism of antibiotic-induced hypokalemic metabolic alkalosis is discussed. It is suggested that most cases of antibiotic-induced hypokalemia respond to oral or intravenous potassium chloride.     

Survival and complete recovery after severe acute ethylen glycol poisoning — a case report

Early signs of acute ethylene glycol (EG) poisoning are similar to ethanol intoxication. However, such signs of EG poisoning are followed by severe metabolic acidosis, increased anion gap, neurological and renal dysfunction, and, without adequate therapy, up to 40% mortality. Early recognition and treatment with intravenous ethanol or fomepizole and bicarbonate, renal replacement therapy, and supportive measures are the key elements of survival.     

Hypokalemia: a practical approach to diagnosis and its genetic basis

Hypokalemia is a common and important finding in hospitalized patients because it may provoke cardiac arrhythmias and/or respiratory arrest. Our aim is to suggest better diagnostic tools and therapeutic principles, and summarize new molecular advances that are linked to hypokalemia. Measurements in freshly-voided urine to evaluate potassium (K+) excretion and an assessment of the acid-base status in blood can help differentiate between the various causes of hypokalemia. In patients with a low rate of K+ excretion, hypokalemia can be explained by an acute shift of K+ into cells, intestinal K+ loss, or prior renal K+ excretion. Patients with a high rate of K+ excretion usually have metabolic acid-base disorders. In patients with hyperchloremic metabolic acidosis, an assessment of the rate of excretion of ammonium (NH4+) in the urine separates those with renal tubular acidosis (RTA) (low NH4+ excretion) from those with causes other than RTA. In patients with metabolic alkalosis, a high blood pressure helps to distinguish between a state with high mineralocorticoid activity from others with extracellular fluid (ECF) volume contraction. Measurement of renin activity, aldosterone, and cortisol levels in plasma help to differentiate between the causes with mineralocorticoid excess whereas the urine chloride (Cl-) concentration may reveal the basis for renal Na+ wasting and distinguish it from non-renal Na+ loss. The treatment of hypokalemia is guided by the risk imposed by hypokalemia, magnitude of the K+ deficit, route of the K+ administration, available K+ preparations, adjuncts to therapy, and special associated conditions. Recent molecular advances in inherited hypokalemic disorders affecting transcellular K+ shift, gastrointestinal and renal K+ excretion are also discussed.     

Nutritional support of patients with renal disease

Current concepts in the nutritional support of patients with renal disease are reviewed. In chronic renal failure, alterations in fat, carbohydrate, and glycogen metabolism usually occur and may be worsened by acute illness. Total parenteral nutrient (TPN) therapy is rarely required unless complications occur. In contrast, acute renal failure is generally associated with hypovolemia, sepsis, soft tissue injury, and coagulation defects, all of which influence metabolism and extracellular fluid volume; the gluconeogenesis that often occurs in these patients masks the metabolic effects of uremia. Nutritional support of patients with renal disease aims at providing adequate nutrients while limiting accumulation of nitrogenous waste. Current concepts concerning essential amino acids (EAAs), nonessential amino acids (NEAAs), and urea recycling are reviewed. The caloric needs of patients with renal failure are assumed to be similar to those of other hospitalized patients. There is no clinically important advantage of using an EAA formulation rather than mixed (EAA and NEAA) amino acids. Since fluid restriction is recommended and protein use is improved with diets with a high calorie-to-nitrogen ratio, the use of TPN solutions with dextrose 350 g is recommended. If glucose intolerance is severe, fat should be considered as a calorie source. Recommendations for monitoring the metabolic status of patients with renal failure receiving nutritional support are reviewed. Monitoring the metabolic status of patients with renal disease is crucial to providing safe and effective nutritional therapy. There appears to be no clinically important advantage to amino acid products specially formulated for use in renal disease.     

Pharmacologic,Pharmacokinetic, and Therapeutic Differences among ACE Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are a heterogeneous group of agents, and important pharmacologic, pharmacokinetic, and therapeutic differences among them must be understood to obtain optimal therapy. For patients with severe liver disease, lisinopril and captopril are not prodrugs (e.g., do not require hepatic activation), and lisinopril has almost solely renal elimination. Enalaprilat, the intravenous formulation of enalapril, is the only intravenously available ACE inhibitor and can be given to patients with severe liver dysfunction as it is also not a prodrug. Fosinopril is the only drug with compensatory dual routes of elimination, and it does not require dosage adjustment in patients with reduced renal function, as other ACE inhibitors do. Captopril and moexipril have potential drug-food interactions and are the only agents that should be spaced from meals. The ACE inhibitors also differ in their dialyzability, half-life, lipophilicity, trough:peak ratios, approved indications, and therapeutic information available for many indications.     

Prevention of metabolic alkalosis induced by gastric fluid loss using H2 receptor antagonist

Gastric fluid loss is a common cause of metabolic alkalosis. We studied various acid-base parameters in 20 patients undergoing continuous nasogastric (NG) suctioning for periods ranging from 3 to 17 days. Ten patients received cimetidine 300 mg intravenously every 6 hr (cimetidine-treated group). The remaining 10 patients received an antacid compound through the NG tube (control group). The rise in plasma bicarbonate concentration was significantly greater in the control group as compared to the cimetidine-treated group. As expected, gastric acid output was considerably lower in the cimetidine-treated group than in the control group. We conclude that cimetidine administration may be used in preventing metabolic alkalosis associated with gastric fluid loss by inhibiting gastric secretion of HCl.     

Famotidine-associated mental confusion in elderly patients

Central nervous system effects, such as mental confusion and hallucinations, have been reported with both cimetidine and ranitidine. Elderly patients with renal or hepatic dysfunction are more susceptible to these adverse reactions. We report two cases of reversible mental confusion in elderly patients with mild renal insufficiency following intravenous famotidine therapy, possibly explained by an increased permeability of the blood-brain barrier in patients with decreased renal function.     

New management options for end-stage chronic liver disease and acute liver failure: potential for pediatric patients

The management of children with end-stage chronic liver disease and acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but studies and publications have mainly concerned adult patients. Therapeutic approaches to complications of end-stage chronic liver disease and acute liver failure (e.g. refractory ascites, hepatorenal syndrome, encephalopathy, and cerebral edema) that may be applied to children are reviewed in this article.Mild-to-moderate ascites should be managed by modest salt restriction and oral diuretic therapy in the first instance. Large volume paracentesis associated with colloid volume expansion and diuretic therapy may be effective for acute relief. Treatment of hepatorenal syndrome type 1 with vasopressin analogs (terlipressin) is recommended prior to liver transplantation in order to improve renal function. Prevention and treatment of chronic hepatic encephalopathy are directed primarily at controlling the events that may precipitate hepatic encephalopathy and at reducing ammonia generation and increasing its detoxification or removal. In addition to reduction of gut ammonia production using non-absorbable disaccharides such as lactulose and/or antibacterials such as neomycin, sodium benzoate may be used on a long-term basis to prevent, stabilize, or improve hepatic encephalopathy. The management of hepatic encephalopathy in acute liver failure is considerably more unsatisfactory; treatment is aimed at preventing brain edema and intracranial hypertension. Extracorporeal liver support devices are now used commonly in critically ill children with acute renal failure, advanced hepatic encephalopathy, cerebral edema, intracranial hypertension, and severe coagulopathy. Continuous renal replacement therapy could potentially help support patients until liver transplantation is performed or liver regeneration occurs. The Molecular Adsorbent Recirculating System (MARS or albumin dialysis) is the liver support system most frequently used worldwide in adults and appears to offer distinct advantages over hepatocyte-based systems.There are no specific medical therapies or devices that can correct all of the functions of the liver. Apart from a few metabolic diseases presenting with severe liver dysfunction for which specific medical therapies may preclude the need for liver transplantation, liver transplantation still remains the only definitive therapy in most instances of end-stage chronic liver disease and acute liver failure. Future research should focus on gaining a better understanding of the mechanisms responsible for liver cell death and liver regeneration, as well as developments in hepatocyte transplantation and liver-directed gene therapy.     

Trovafloxacin: An Overview

Trovafloxacin, a new synthetic naphthyridine fluoroquinolone antibiotic, is a broad-spectrum agent available orally and intravenously. It was recently approved by the Food and Drug Administration for the treatment of selected pulmonary, surgical, intraabdominal, gynecologic, pelvic, skin, and urinary tract infections. Its spectrum of activity includes aerobic gram-positive and gram-negative organisms as well as anaerobic pathogens. It is rapidly absorbed after oral administration, achieves good tissue and cerebrospinal fluid penetration, and has a half-life that allows once-daily dosing. It is hepatically metabolized, and dosage adjustments are necessary for patients with severe hepatic dysfunction but not for those with mild or moderate dysfunction or renal dysfunction. The drug has a favorable safety profile, and a high tendency for transient first-dose dizziness and/or lightheadedness in young women. Similar to other quinolones, trovafloxacin should not be taken with antacids that contain aluminum or magnesium, sucralfate, or ferrous sulfate. Trovafloxacin may prove beneficial as it allows for oral or intravenous monotherapy against indicated infections that normally require multidrug, broad-spectrum antibiotic coverage.     

Management of diabetic ketoacidosis in children and adolescents

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus. While it can occur in all types of diabetes mellitus, it is seen most often in patients with type 1 diabetes, either at presentation or as a result of non-compliance with medical therapy. DKA is characterized by hyperglycemia, acidosis, dehydration, and electrolyte abnormalities, which result from a deficiency of insulin and an excess of counter-regulatory hormones.Therapy is aimed at repleting fluids, and correcting acidosis and electrolyte disturbances by administration of intravenous fluid and intravenous insulin. Rapid correction should be avoided as it may result in untoward effects, including cerebral edema. Frequent monitoring of neurologic status and metabolic parameters aids in avoidance or early detection of complications. While much is still not understood about the most serious complication, cerebral edema, recent studies suggest that its development may be tied to a loss of cerebral autoregulation and a vasogenic mechanism of edema formation. Treatment of cerebral edema includes fluid restriction and administration of mannitol. Once DKA has resolved, subcutaneous insulin is initiated with careful consideration of its pharmacokinetics to avoid a period of insulin deficiency and metabolic decompensation.     

醋酸钠林格液用于围术期容量治疗的随机对照临床研究

目的评价醋酸钠林格液用于围术期容量治疗的有效性和安全性。方法本研究为随机、对照、双盲研究。选择需要输液的择期手术患者80例,ASAⅠ～Ⅱ级,年龄18～65岁,随机分为2组(n=40),醋酸钠林格液组(AR组)和乳酸钠林格液组(LR组),病人建立静脉通路后2 h内输注试验药或对照药2 L,作为血容量补充剂。观察生命体征的稳定性、血管活性药物的使用频次、酸碱和离子平衡以及血尿常规、肝肾功能和凝血功能等指标。结果各时间点收缩压、舒张压和心率,两组间比较差异无统计学意义(P>0.05);两组的血管活性药物的使用频次差异无统计学意义(P>0.05);治疗结束时两组收缩压稳定律的比较差异无统计学意义(P>0.05);给药后两组pH值与实际碱剩余(ABE)值变化差异有统计学意义(P<0.05)。结论醋酸林格注射液能有效用于围术期容量治疗,与乳酸钠林格注射液相比,其在维持血流动力学稳定及电解质平衡方面无显著性差异,但输注后pH值与ABE值高于乳酸钠林格液,用于治疗乳酸血症、酸中毒和缺氧或氧代谢异常者应更有优势。     

Management of acute kidney injury in children: a guide for pediatricians

Acute kidney injury (AKI; previously called acute renal failure) is characterized by a usually reversible increase in the blood concentration of creatinine and nitrogenous waste products and by the inability of the kidney to appropriately regulate fluid and electrolyte homeostasis. The incidence of AKI in children appears to be increasing and the etiology of AKI over the past decades has shifted from primary renal disease to multifactorial causes, particularly in hospitalized children. Renal failure can be divided into prerenal failure, intrinsic renal disease including vascular insults, and obstructive uropathies. The history, physical examination, and laboratory studies including a urinalysis and radiographic studies can establish the likely cause(s) of AKI. Once intrinsic renal failure has become established, management of the metabolic complications of AKI requires meticulous attention to fluid balance, electrolyte status, acid-base balance, and nutrition. Many children with AKI will need renal replacement therapy to remove endogenous and exogenous toxins and to maintain fluid, electrolyte, and acid-base balance until renal function improves. Renal replacement therapy may be provided by peritoneal dialysis (PD), intermittent hemodialysis (HD), or hemofiltration with or without a dialysis circuit. Many factors--including the age and size of the child, the cause of renal failure, the degree of metabolic derangements, blood pressure, and nutritional needs--are considered in deciding when to initiate renal replacement therapy and which modality of therapy to use. The prognosis of AKI is highly dependent on the underlying etiology of the AKI. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease. Recovery from intrinsic renal disease is also highly dependent on the underlying etiology of the AKI. Children who have experienced AKI from any cause are at risk for late development of renal failure long after the initial insult. Such children need life-long monitoring of their renal function, blood pressure, and urinalysis.     

Chronic salicylism in a patient with juvenile rheumatoid arthritis

A patient who developed chronic salicylism associated with salicylate therapy for treatment of juvenile rheumatoid arthritis is described, and the clinical presentation and treatment of chronic salicylism are reviewed. A 5 1/2-year-old boy was receiving aspirin 150/mg/kg/day for treatment of juvenile rheumatoid arthritis. While on salicylate therapy, the patient developed tachypnea and became increasingly hyperthermic, lethargic, and disoriented. The patient developed a maculopapular rash, weakness, and a decreased level of consciousness during the 11 days before admission to the hospital. Physical examination and laboratory determinations revealed that the patient had hypoprothrombinemia, hypoglycemia, and severe hepatic encephalopathy secondary to long-term salicylate toxicity. The patient was treated for hypoglycemia, electrolyte imbalances, thrombocytopenia, and anemia and was discharged after 24 days. Diagnosing chronic salicylism with hepatic dysfunction was difficult because the symptoms are similar to those of stage I to stage II Reye's syndrome. Liver enzymes, including aspartate aminotransferase (also called SGOT), alanine aminotransferase (also called SGPT), alkaline phosphatase, and lactate dehydrogenase, may be elevated in juvenile arthritis patients with hepatic dysfunction. Liver dysfunction usually improves when salicylate therapy is discontinued. Supportive therapy should always be used in symptomatic patients. Children on long-term, high-dose salicylate therapy should be monitored closely, and baseline liver function tests should be performed. The clinical effectiveness of administering sodium bicarbonate in attempts to alkalinize urine and increase salicylate elimination is controversial. In patients with juvenile rheumatoid arthritis who develop chronic salicylism, careful analysis of the patient's medication history, laboratory values, and clinical presentation are necessary to rule out Reye's syndrome.     

Subclinical tumor lysis-like syndrome during treatment of visceral leishmaniasis with low-dose intermittent liposomal amphotericin B

We retrospectively evaluated the rate of renal dysfunction during treatment with liposomal amphotericin B (L-AmB) (3–4 mg/kg, for 7–10 days) in nine consecutive patients with visceral leishmaniasis (VL). During the first week of treatment, 5 patients (56%) experienced transient deterioration of renal function, with a rise in serum creatinine to 1.27–2.44 times the baseline level, and a parallel elevation of uric acid levels without other metabolic or electrolyte disturbances. Serum renal function parameters were restored to normal levels after the completion of therapy, on day 21. These 5 patients had presented with prolonged fever and/or significant spleen enlargement, reflecting high parasite load. This observation suggests that treatment of VL with intermittent L-AmB causes a subclinical tumor lysis-like syndrome, especially in patients with high parasite load.     

Errors in fluid therapy in medical wards

Background Intravenous fluid therapy remains an essential part of patients?? care during hospitalization. There are only few studies that focused on fluid therapy in the hospitalized patients, and there is not any consensus statement about fluid therapy in patients who are hospitalized in medical wards. Objective The aim of the present study was to assess intravenous fluid therapy status and related errors in the patients during the course of hospitalization in the infectious diseases wards of a referral teaching hospital. Setting This study was conducted in the infectious diseases wards of Imam Khomeini Complex Hospital, Tehran, Iran. Methods During a retrospective study, data related to intravenous fluid therapy were collected by two clinical pharmacists of infectious diseases from 2008 to 2010. Intravenous fluid therapy information including indication, type, volume and rate of fluid administration was recorded for each patient. An internal protocol for intravenous fluid therapy was designed based on literature review and available recommendations. The data related to patients?? fluid therapy were compared with this protocol. The fluid therapy was considered appropriate if it was compatible with the protocol regarding indication of intravenous fluid therapy, type, electrolyte content and rate of fluid administration. Main outcome measure: Any mistake in the selection of fluid type, content, volume and rate of administration was considered as intravenous fluid therapy errors. Results Five hundred and ninety-six of medication errors were detected during the study period in the patients. Overall rate of fluid therapy errors was 1.3 numbers per patient during hospitalization. Errors in the rate of fluid administration (29.8%), incorrect fluid volume calculation (26.5%) and incorrect type of fluid selection (24.6%) were the most common types of errors. The patients?? male sex, old age, baseline renal diseases, diabetes co-morbidity, and hospitalization due to endocarditis, HIV infection and sepsis are predisposing factors for the occurrence of fluid therapy errors in the patients. Conclusion Our result showed that intravenous fluid therapy errors occurred commonly in the hospitalized patients especially in the medical wards. Improvement in knowledge and attention of health-care workers about these errors are essential for preventing of medication errors in aspect of fluid therapy.     

应用羟乙基淀粉130/0.4液体复苏治疗重症急性胰腺炎患者的临床观察

目的:探讨羟乙基淀粉130/0.4(万汶)对重症急性胰腺炎(SAP)患者进行液体复苏的有效性和安全性。方法:我院2006年6月～2007年12月收治的40例未手术的急性重症胰腺炎患者,用随机单盲的方法分成两组,万汶组20例,林格液组2O例。两组均禁食、胃肠减压、纠正水电解质酸碱平衡紊乱、静脉营养支持、制酸、生长抑素及抗生素应用,其中万汶组每日万汶15 ml/kg静脉滴注,疗程5 d;林格液组每日林格液20 ml/kg静脉滴注,疗程5 d。观察两组疗效、血液流变学、凝血功能、肾功能以及肺部并发症。结果:万汶组治疗有效率高,肺部并发症发生率低,明显优于林格液组。万汶组血液流变学参数改善差异有显著性(P<0.05),而林格液组变化差异无显著性(P>0.05);两组的凝血功能和肾功能在复苏前后差异无显著性(P>0.05)。结论:万汶能快速有效地稳定血流动力学,改善血液流变学,可能更有利于改善胰腺微循环障碍,故可首先考虑用于SAP患者的液体复苏。     

Treatment of severe cryptosporidium-related diarrhea with octreotide in a patient with AIDS

Cryptosporidiosis commonly causes severe diarrhea in immunosuppressed patients. There currently are no antiparasitic drugs consistently effective for this infection. This case describes a 26-year-old hemophiliac patient with acquired immunodeficiency syndrome and cryptosporidiosis whose diarrhea improved with continuous intravenous administration of a long-acting somatostatin analog, octreotide. Somatostatin has a variety of inhibitory effects on gastrointestinal hormones as well as a possible nonspecific effect on gastrointestinal mucosal fluid and electrolyte secretion. The somatostatin analog should be considered for patients with secretory diarrhea refractory to other forms of therapy.