sodium-bicarbonate and Hypotension

This review aimed to explore and summarize information from available cases of pediatric acute hydroxychloroquine overdose with confirmed hydroxychloroquine exposure to give the clinicians a helpful perspective for its better recognition and management.. Electronic searches were conducted in PubMed/MEDLINE, Web of Science, Scopus, EBSCO and Serbian Citation Index. The abstracts from 2 toxicology conferences were manually checked for additional relevant publications, as well as reference lists of the retrieved publications. Descriptive statistics, narrative summation, and tabulation of the extracted data were made.. Nine publications and a total of 9 patients were included in the review. Reported age of the patients varied from 2.5 to 16 years (median, 16 years). There were more female patients (77.8%). Estimated total ingested hydroxychloroquine dose was reported in 7 cases (77.8%), and it ranged from 4.0 to 20.0 g (median: 12.0 g). Four patients (44.4%) ingested hydroxychloroquine with a coingestant. Altered mental status (100.0%), cardiotoxicity (88.9%), hypotension (77.8%), and hypokalemia (55.6%) were the most commonly reported clinical manifestations. The majority of the patients were hospitalized (88.9%). More than half of the patients (55.6%) were reported to be treated in the intensive care unit. Most frequently reported therapeutic measures were the following: administration of intravenous fluids/infusions (77.8%), vasopressors (77.8%), bicarbonate therapy-sodium bicarbonate (66.7%), potassium replacement (55.6%), and intubation/ventilation (55.6%). Three patients (33.3%) died.. Management of acute hydroxychloroquine overdose in children should be symptomatic and tailored to observed clinical manifestations. There is a need for additional investigations to better understand the impact and effectiveness of various treatment options.

Topics: Adolescent; Child; Child, Preschool; Drug Overdose; Female; Humans; Hydroxychloroquine; Hypotension; Sodium Bicarbonate; Vasoconstrictor Agents

Experimental studies suggest that both alkalinisation and sodium loading are effective in reducing cardiotoxicity independently. Species and experimental differences may explain why sodium bicarbonate appears to work by sodium loading in some studies and by a pH change in others. In the only case series, the administration of intravenous sodium bicarbonate to achieve a systemic pH of 7.5-7.55 reduced QRS prolongation, reversed hypotension (although colloid was also given) and improved mental status in patients with moderate to severe tricyclic antidepressant poisoning. This clinical study supports the use of sodium bicarbonate in the management of the cardiovascular complications of tricyclic antidepressant poisoning. However, the clinical indications and dosing recommendations remain to be clarified. Hypotension should be managed initially by administration of colloid or crystalloid solutions, guided by central venous pressure monitoring. Based on experimental and clinical studies, sodium bicarbonate should then be administered. If hypotension persists despite adequate filling pressure and sodium bicarbonate administration, inotropic support should be initiated. In a non-randomised controlled trial in rats, epinephrine resulted in a higher survival rate and was superior to norepinephrine both when the drugs were used alone or when epinephrine was used in combination with sodium bicarbonate. Sodium bicarbonate alone resulted in a modest increase in survival rate but this increased markedly when sodium bicarbonate was used with epinephrine or norepinephrine. Clinical studies suggest benefit from norepinephrine and dopamine; in an uncontrolled study the former appeared more effective. Glucagon has also been of benefit. Experimental studies suggest extracorporeal circulation membrane oxygenation is also of potential value. The immediate treatment of arrhythmias involves correcting hypoxia, electrolyte abnormalities, hypotension and acidosis. Administration of sodium bicarbonate may resolve arrhythmias even in the absence of acidosis and, only if this therapy fails, should conventional antiarrhythmic drugs be used. The class 1b agent phenytoin may reverse conduction defects and may be used for resistant ventricular tachycardia. There is also limited evidence for benefit from magnesium infusion. However, class 1a and 1c antiarrhythmic drugs should be avoided since they worsen sodium channel blockade, further slow conduction velocity and depress contractility.

Topics: Alkalosis, Respiratory; Anti-Arrhythmia Agents; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Humans; Hypotension; Poisoning; Sodium Bicarbonate

Sodium bicarbonate infusion is widely recommended in textbooks for patients who present with self-poisoning from tricyclic antidepressives. Cardiac conduction disorders could also be treated or prevented by means of such an infusion. The scientific basis for these recommendations was investigated by using Medline to search for publications about clinical studies that supported the use of sodium carbonate; 111 articles were scrutinized. Observational studies and case reports mention a rapid improvement in hypotension and cardiac arrhythmias following the administration of sodium bicarbonate. Results from animal experiments are contentious; it is not clear whether alkalinisation or the administration of extra sodium causes the effect. Randomized studies in patients have not been carried out. As the toxicity of sodium bicarbonate is low, and its potential benefit appears to be high, we recommend its use, despite the lack of scientific evidence. No recommendations concerning dosing, concentration and the length of the therapy can be provided on the basis of the literature.

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Drug Overdose; Female; Humans; Hypotension; Infusions, Intravenous; Retrospective Studies; Sodium Bicarbonate

Poisoning with flecainide acetate is rare and associated with a high mortality. This usually occurs after massive ingestion but can also be observed during therapeutic overdose in patients with renal failure or with amiodarone therapy. The prognostic depends on the haemodynamic and rhythmic effects of the overdose one sign of which is widening of the QRS complexes. Major sodium bicarbonate or lactate infusion is the generally prescribed treatment. The authors report one case of a patient with renal failure on amiodarone who survived a severe flecainide acetate overdose.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Atrial Flutter; Biological Availability; Calcium Gluconate; Charcoal; Combined Modality Therapy; Consciousness Disorders; Diabetic Nephropathies; Drug Interactions; Drug Therapy, Combination; Flecainide; Heart Block; Hemofiltration; Humans; Hypertension; Hypotension; Intestinal Pseudo-Obstruction; Kidney Failure, Chronic; Male; Poisoning; Pulmonary Edema; Renal Dialysis; Respiration, Artificial; Sodium Bicarbonate; Sodium Channel Blockers; Uremia

Topics: Animals; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cardiovascular Diseases; Child, Preschool; Drug Overdose; Female; Humans; Hypertonic Solutions; Hypotension; Infant, Newborn; Sodium Bicarbonate

The use of bicarbonate dialysate as the buffer during routine dialysis is growing. This discussion reviews several of the comparative trials in which bicarbonate and acetate buffers have been tested. Effects of the two buffers on BP, cardiac function, and pulmonary performance are discussed. Costs of the two systems are also compared. Patients who seem most likely to benefit from bicarbonate dialysate include those with a reduced muscle mass in whom a high sodium dialysate has not prevented hypotension.

Topics: Acetates; Acetic Acid; Bicarbonates; Buffers; Humans; Hypotension; Hypoxia; Myocardial Contraction; Renal Dialysis; Sodium; Sodium Bicarbonate

More than 6 per cent of poisonings involve alcohols and glycols, reflecting their availability in a wide range of household products, including aftershave, brake fluid, gas line antifreeze, model airplane fuel, mouthwash, rubbing alcohol, and windshield washing solution. Diagnosis involves recognition of an osmolal gap and variable degrees and delays in development of an anion gap metabolic acidosis. Therapeutic modalities are similar for methanol and ethylene glycol, both cases requiring ethanol-blocking of alcohol dehydrogenase and hemodialysis. More often, treatment of ethanol and isopropanol poisoning is limited to supportive care.

Topics: 1-Propanol; Absorption; Acidosis; Adult; Alcoholic Intoxication; Bicarbonates; Blindness; Child; Child, Preschool; Diagnosis, Differential; Ethylene Glycol; Ethylene Glycols; Gastric Lavage; Humans; Hypotension; Infant; Ipecac; Kidney Diseases; Kinetics; Liver; Methanol; Mortality; Osmolar Concentration; Renal Dialysis; Sodium; Sodium Bicarbonate

Diphenhydramine is a moderately lipophilic antihistamine with sodium channel blockade properties. It is consumed recreationally for mild hallucinogenic and hypnotic effects and causes dysrhythmias, seizures, and death with overdose. Intravenous lipid emulsion is a novel agent used to treat lipophilic drug overdose. Two case reports describe clinical improvement with intravenous lipid emulsion after diphenhydramine toxicity, but no prospective studies have been reported. Our objective is to determine whether intravenous lipid emulsion improved hypotension compared with sodium bicarbonate for severe diphenhydramine toxicity in a model of critically ill swine.. Twenty-four swine weighing 45 to 55 kg were infused with diphenhydramine at 1 mg/kg per minute until the mean arterial pressure reached 60% of baseline. Subjects were randomized to receive intravenous lipid emulsion (bolus of 7 mL/kg and then 0.25 mL/kg per minute) or sodium bicarbonate (2 mEq/kg plus an equal volume of normal saline solution). We measured pulse rate, systolic blood pressure, mean arterial pressure, cardiac output, QRS interval, and serum diphenhydramine level. Twelve animals per group provided a power of 0.8 and α of .05 to detect a 50% difference in mean arterial pressure. We assessed differences between groups with a repeated-measures linear model (MIXED) and Kaplan-Meier estimation methods. We compared systolic blood pressure, mean arterial pressure, and cardiac output with repeated measures ANOVA.. Baseline weight, hemodynamic parameters, QRS interval, time to hypotension, and diphenhydramine dose required to achieve hypotension were similar between groups. After hypotension was reached, there was no overall difference between intravenous lipid emulsion and sodium bicarbonate groups for cardiac output or QRS intervals; however, there were transient differences in mean arterial pressure and systolic blood pressure, favoring intravenous lipid emulsion (difference: mean arterial pressure, sodium bicarbonate versus intravenous lipid emulsion -20.7 [95% confidence interval -31.6 to -9.8]; systolic blood pressure, sodium bicarbonate versus intravenous lipid emulsion -24.8 [95% confidence interval -37.6 to -12.1]). Time to death was similar. One intravenous lipid emulsion and 2 sodium bicarbonate pigs survived. End-of-study mean total serum diphenhydramine levels were similar. The mean lipid layer diphenhydramine level was 6.8 μg/mL (SD 3.1 μg/mL) and mean aqueous layer level 8.6 μg/mL (SD 5.5 μg/mL).. In our study of diphenhydramine-induced hypotensive swine, we found no difference in hypotension, QRS widening, or diphenhydramine levels in aqueous layers between intravenous lipid emulsion and sodium bicarbonate.

Topics: Animals; Diphenhydramine; Disease Models, Animal; Fat Emulsions, Intravenous; Female; Hemodynamics; Hypotension; Pilot Projects; Sodium Bicarbonate; Swine

Metformin is an antidiabetic drug; used to treat type II diabetes mellitus, metformin associated lactic acidosis has an incidence of 2-9 cases / 100,000 patients / year with high mortality (30%). We have had the case of a 75-year-old woman with metabolic acidosis as a result of metformin assumption, treated by renal replacement therapy (CRRT) with continuous veno-venous hemodiafiltration (CVVHDF).. after a short treatment period there was a reduction in Lactates (from 16.8 mmol/L to 12.6 mmol/L) and a progressive improvement of acidosis. In 72 hours the recovery of diuresis and subsequent suspension of CRRT was achieved.. CRRT, in addition to ensuring support for renal failure and volume correction, allowed a rapid recovery from metformin-associated lactic acidosis.

Topics: Acidosis, Lactic; Aged; Anticoagulants; Bronchial Spasm; Combined Modality Therapy; Female; Furosemide; Hemodiafiltration; Humans; Hypoglycemic Agents; Hypotension; Metformin; Piperacillin, Tazobactam Drug Combination; Sodium Bicarbonate; Sodium Citrate

Topics: Acidosis; Adolescent; Antidepressive Agents, Tricyclic; Drug Overdose; Female; Humans; Hypokalemia; Hypotension; Pneumonia; Respiration, Artificial; Respiratory Distress Syndrome; Sodium Acetate; Sodium Bicarbonate; Suicide, Attempted; Vasoconstrictor Agents

We report a rare fatal case of acute metformin overdose in a 19-year-old woman.

Topics: Acidosis; Blood Gas Analysis; Cardiotonic Agents; Drug Overdose; Fatal Outcome; Female; Heart Arrest; Humans; Hypoglycemia; Hypoglycemic Agents; Hypotension; Long QT Syndrome; Metformin; Sodium Bicarbonate; Young Adult

This case report describes the possible benefit of intravenous lipid emulsion in two patients surviving a severe intoxication with hydroxychloroquine in a dose that was previously considered to be lethal. The first case involves a 25-year-old female who ingested 17.5 grams of hydroxychloroquine, approximately one hour before presentation. An ECG showed QRS widening and the lab results showed hypokalaemia. She became unconscious, and developed hypotension and eventually apnoea. After intubation, supportive care consisted of norepinephrine and supplementation of potassium. Moreover, sodium bicarbonate and intravenous lipid emulsion were started to prevent cardiac toxicity. After these interventions, haemodynamic stability was established within a few hours. Although cardiomyopathy was confirmed, the patient recovered after two weeks. The second case concerns a 25-year-old male who took 5 grams of hydroxychloroquine. At presentation, two hours after intake, he showed QTc prolongation and hypokalaemia. The patient was treated with the usual supportive care and, although presentation to hospital was later, with intravenous lipid emulsion. Also this patient recovered. In conclusion, these cases show the benefit of supplemental intravenous lipid emulsion to prevent cardiac toxicity after a severe intoxication with hydroxychloroquine.

Topics: Adult; Arrhythmias, Cardiac; Chromatography, Liquid; Drug Overdose; Electrocardiography; Fat Emulsions, Intravenous; Female; Humans; Hydroxychloroquine; Hypokalemia; Hypotension; Male; Norepinephrine; Potassium Chloride; Sodium Bicarbonate; Suicide, Attempted; Tandem Mass Spectrometry; Vasoconstrictor Agents

Tricyclic antidepressants (TCAs) are highly lipophilic medications used to treat posttraumatic stress disorder and chronic pain. Intravenous lipid emulsion (ILE) is a recent antidote for lipophilic drug overdose with unclear effectiveness. ILE has been studied in TCA overdose in small animals, and cases are reported in humans, but controlled studies in a larger animal model are lacking. Given the high lipophilicity of amitriptyline, a TCA, the hypothesis was that ILE would be more effective than the standard antidote sodium bicarbonate in improving amitriptyline-induced hypotension. The objective was to determine if ILE improved hypotension (defined by a mean arterial pressure [MAP] < 60% baseline) compared to sodium bicarbonate for amitriptyline overdose in a critically ill porcine model.. In this prospective, randomized, controlled trial, 24 female Sus scrofa swine weighing 45 to 55 kg were infused with amitriptyline at 0.5 mg/kg/min until the MAP reached 60% of baseline values. Animals were randomized to the experimental treatment group (ILE 7 mL/kg bolus, then 0.25 mL/kg/min) or the standard treatment group (sodium bicarbonate 2 mEq/kg plus an equal volume of saline). The primary outcome was a 50% improvement in MAP after ILE administration. We continuously monitored heart rate (HR), systolic blood pressure (sBP), MAP, and cardiac output. Electrocardiograms were recorded every 15 minutes. Serum pH, pCO2 , bicarbonate, lactate, and electrolytes were measured. Amitriptyline levels were measured by liquid chromatography/tandem mass spectrometry. Statistical methods used to detect a difference in MAP between the two treatment groups included repeated-measures analysis of variance, adjusted for treatment, time, and the interaction of treatment by time. A sample size of 12 animals per group provided a power of 0.8 and an alpha of 0.05 to detect a 50% difference in MAP.. There was no difference at baseline between ILE and sodium bicarbonate groups in mean HR, sBP, MAP, or cardiac output. Mean amounts of amitriptyline to reach hypotension and time to hypotension were similar between groups. After hypotension there was no difference between groups for mean HR, sBP, MAP, or cardiac output. The median time from hypotension to death was greater for the sodium bicarbonate group (10 minutes [IQR = 6 to 61 minutes] vs. 5 minutes [IQR = 4.5 to 6 minutes] for the ILE group; p = 0.003), but overall survival was not different. One ILE and four sodium bicarbonate pigs survived. Additionally, no difference was detected in QRS intervals between the two groups. The mean (±SD) amitriptyline level in the lipid layer was 3.34 (±2.12) μg/mL, and in the aqueous layer, 4.69 (±2.44) μg/mL. The ILE fatty layer contained 38.2% of total measurable amitriptyline, while the aqueous layer contained 53.6%.. Intravenous lipid emulsion treatment failed to improve amitriptyline-induced hypotension when compared to the standard treatment of sodium bicarbonate in a large animal model of severe TCA overdose. Larger groups with better survival may yield different results from the high mortality observed in this pilot study. Similar amounts of amitriptyline were found in the aqueous and lipid layers. These conclusions are limited to a single ILE regimen.

Topics: Animals; Antidepressive Agents, Tricyclic; Blood Pressure; Disease Models, Animal; Fat Emulsions, Intravenous; Female; Hypotension; Pilot Projects; Prospective Studies; Sodium Bicarbonate; Swine

Intravenous fat emulsion (IFE) is emerging as a novel antidote in clinical toxicology. Its current usage is extending beyond local anaesthetic toxicity into management of severe toxicity from some lipophilic drugs. We present a 51-year-old woman with severe bupropion toxicity whose haemodynamic status transiently improved after IFE. Serum analysis demonstrated an increase in serum concentration of hydroxybupropion, an active metabolite of bupropion, after IFE administration, lending support to one of the proposed mechanisms of IFE. A 51-year-old woman presented to the emergency department with generalised tonic-clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium bicarbonate therapy, the patient developed profound hypotension refractory to high-dose norepinephrine. IFE was administered with haemodynamic improvement over the course of 30 min., followed by a significant decrease in norepinephrine requirement. The patient had an episode of ventricular tachycardia 24 hr after presentation, and received a second infusion of IFE. Analysis of serum for a panel of myocardial sodium channel blocking drugs revealed that significant bupropion ingestion had occurred. Bupropion poisoning may produce life-threatening clinical effects, and IFE may be considered in cases of severe haemodynamic instability. Further studies would be instrumental in determining the optimal clinical situations for utilisation of IFE.

Topics: Antidotes; Bupropion; Eating; Electrocardiography; Fat Emulsions, Intravenous; Female; Humans; Hypotension; Middle Aged; Sodium Bicarbonate; Tachycardia, Ventricular

Metformin, widely used in the treatment of diabetes mellitus, is known to cause lactic acidosis in both therapeutic use and after an overdose. We report the case of a 40-year-old woman who claimed to have ingested between 75 and 100 grams of metformin and subsequently developed severe lactic acidosis. She eventually developed a peak serum lactate level of 40.0 mmol/L and a serum pH nadir of 6.59 and became obtunded, hypotensive, and hypothermic. After aggressive supportive therapy with mechanical ventilation, vasopressor agents, sodium bicarbonate, and hemodialysis, her metabolic derangements steadily improved and she made a complete recovery without any residual sequelae. Her admission serum metformin concentration was later determined to be 160 microg/mL (therapeutic range is 1-2 microg/mL). There are several case reports and case series describing lactic acidosis secondary to metformin ingestion, although the exact mechanism remains unclear. The overall management of metformin overdose is reviewed. This case represents the largest reported amount of ingested metformin, the lowest serum pH, and the highest serum lactate concentration in any intentional metformin overdose survivor in the literature. Despite potentially lethal metabolic derangements, such patients can survive with aggressive supportive care.

Topics: Acidosis, Lactic; Adult; Drug Overdose; Female; Humans; Hypoglycemic Agents; Hypotension; Metformin; Poisoning; Sodium Bicarbonate

Determination of arterial blood gas (ABG) values is essential in the evaluation of patients with TCA poisoning. The relationship between arterial and venous blood gas pH has not been established in TCA poisoning. In TCA poisoning, blood vessels vasodilatation due to antidepressant-induced alpha-blockade and also metabolic acidosis may lead to arterialization of venous blood, which in turn enhances the relationship between ABG and VBG parameters. Therefore this study was designed to evaluate the relationship between ABG and VBG pH values in TCA poisoned patients.. This prospective study was performed in the Poisoning Emergency Department of Noor Hospital, Isfahan, Iran. Samples for arterial and venous blood gas analysis were obtained during initial evaluation of TCA-poisoned patients and 30 min after treatment with sodium bicarbonate. The venous blood gas samples were collected with samples for other blood tests at the time of intravenous line insertion. Laboratory data were recorded on a database form initiated in the emergency department and analyzed by paired student t-test. The degree of agreement between the arterial and venous pH measurements was evaluated by Bland and Altman method.. Data from 50 TCA-poisoned patients were analyzed. There were significant differences between mean differences of ABG and VBG parameter values on the initial evaluation. There was also a relationship between arterial and venous pH on the initial evaluation.. In TCA poisoning, the peripheral venous pH measurement is a valid and reliable substitute for arterial pH.

Topics: Acid-Base Equilibrium; Acidosis; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Blood Gas Analysis; Data Interpretation, Statistical; Diagnostic Tests, Routine; Electrocardiography; Humans; Hydrogen-Ion Concentration; Hypotension; Injections, Intravenous; Patients; Sodium Bicarbonate

We describe a case of medication induced metabolic alkalosis in a maintenance dialysis patient who developed severe hypotension while undergoing a lactate hemofiltration procedure. A 73-year-old man with ESRD due to renovascular disease was used to ingesting up to 30 grams per day of a non-prescription medication (Effervescent granulare 250 grams, CRASTAN, Pisa Italy) consisting of sodium bicarbonate, citric acid, glucose and lemon flavor. For technical problem lactate hemofiltration was performed and thirty minutes after dialysis was started a severe symptomatic hypotension occurred (blood pressure 65/35 mmHg). Lactate hemofiltration was suspended and one-hour later standard bicarbonate dialysis was performed without any clinical problem. The different mechanisms in acidosis buffering occurring in lactate and bicarbonate hemofiltration were discussed.

Topics: Aged; Alkalosis; Hemodiafiltration; Humans; Hypotension; Kidney Failure, Chronic; Male; Severity of Illness Index; Sodium Bicarbonate

This study was conducted to determine whether hypertonic sodium bicarbonate would improve the hypotension associated with severe verapamil toxicity compared with volume expansion.. The study design used a nonblinded acute animal preparation. Twenty-four anesthetized and instrumented swine were poisoned with verapamil delivered at a rate of 1 mg/kg per hour for 10 minutes followed by incremental increases of 1 mg/kg per hour every 10 minutes until the endpoint of a mean arterial blood pressure of 45% of baseline was achieved. Animals alternately received either 4 mEq/kg of hypertonic sodium bicarbonate intravenously over 4 minutes or similar volumes of 0.6% sodium chloride in 10% mannitol (control). The main outcome parameter followed was mean arterial pressure. In addition, physiologic parameters including cardiac output, heart rate, pH, PCO (2), PO (2), plasma ionized calcium, sodium, and potassium were monitored.. Verapamil toxicity, as defined by a mean arterial pressure of 45% of baseline, was produced in all animals following an average verapamil infusion dose of 0.6+/-0.12 mg/kg. This dose produced an average plasma verapamil concentration of 728.1+/-155.4 microgram/L, with no significant difference between groups. Swine treated with hypertonic sodium bicarbonate experienced a significant increase in mean arterial pressure (>50%) and cardiac output (>30%) over the first 20 minutes that slowly equilibrated with the control group over the remainder of the experiment. As expected, plasma sodium concentrations were elevated significantly in the sodium bicarbonate group while plasma potassium concentrations were decreased significantly. Finally, there was a significant decrease in plasma ionized calcium concentration in the sodium bicarbonate-treated group compared with controls.. Hypertonic sodium bicarbonate reversed the hypotension and cardiac output depression of severe verapamil toxicity in a swine model.

Topics: Animals; Blood Pressure Determination; Disease Models, Animal; Drug-Related Side Effects and Adverse Reactions; Hemodynamics; Hypertonic Solutions; Hypotension; Infusions, Intravenous; Male; Reference Values; Severity of Illness Index; Sodium Bicarbonate; Sodium Chloride; Survival Rate; Swine; Verapamil

Hypotension is a major contributor to mortality in tricyclic antidepressant overdose. Recent data suggest that tricyclic antidepressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepressant-induced hypotension.. Two interventions were studied that have been shown previously to improve blood pressure with calcium channel blocker overdose. CaCl2 and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desipramine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline.. NaHCO3 briefly (5 min) reversed hypotension and QRS prolongation. CaCl2 and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2 group was higher than the other groups.. The administration of CaCl2 or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2 therapy may possibly worsen both cardiovascular and central nervous system toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hypotension.

Topics: 4-Aminopyridine; Animals; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Blood Pressure; Bradycardia; Calcium Channels; Calcium Chloride; Desipramine; Disease Models, Animal; Electrocardiography; Hypotension; Male; Rats; Saline Solution, Hypertonic; Sodium Bicarbonate

Episodes of arterial hypotension are associated with an increased mortality in head injury patients. Rapid infusion of sodium bicarbonate in such patients may cause hypotension and elevate intracranial pressure. Therefore, we examined the effects of tromethamine (THAM) versus bicarbonate on intracranial pressure and blood pressure in a model of focal cerebral injury. THAM is a buffer that in previous studies has been shown to lower intracranial pressure. After creation of a cryogenic lesion in 13 New Zealand white rabbits, equivalent infusions (15 s duration) of sodium bicarbonate and THAM (2 mEq/kg) were administered sequentially to each animal in random order. Rapid infusion was chosen to simulate the administration of these drugs during a resuscitation. THAM infusion was associated with a significantly lower intracranial pressure and blood pressure than bicarbonate. The fall in blood pressure was great enough that cerebral perfusion pressure after THAM infusion was significantly lower than after bicarbonate infusion. In this model of cerebral injury, rapid infusion of THAM offered no therapeutic advantage over bicarbonate.

Topics: Animals; Blood Pressure; Brain Injuries; Carbon Dioxide; Cerebrovascular Circulation; Hydrogen-Ion Concentration; Hypotension; Injections, Intravenous; Intracranial Pressure; Osmolar Concentration; Oxygen; Rabbits; Sodium Bicarbonate; Tidal Volume; Tromethamine

The objective of this study was to characterize the effect of intravenous hypertonic sodium bicarbonate (NaHCO3) administration in patients with moderate-to-severe cyclic antidepressant (CA) overdose. We reviewed charts of all 91 patients given the diagnosis of CA overdose in the University of California Los Angeles (UCLA) Emergency Medicine Center (EMC), who either died in the EMC or were admitted to the medical intensive care unit (MICU), and who received NaHCO3 in the EMC between 1980 and 1988. Twenty-four other patients with the same EMC diagnosis were admitted to the MICU during this period but did not receive NaHCO3. The response of blood pressure, electrocardiographic parameters, and mental status to serum alkalinization with NaHCO3 were evaluated. Major morbidity and mortality were recorded for all patients. Hypotension was corrected within 1 hour in 20 of 21 (96%) patients, QRS prolongation corrected in 39 of 49 (80%), and mental status improved in 40 of 85 (47%). There was one death, in a patient who was moribund on arrival to the EMC. No complications were attributable to the administration of NaHCO3. NaHCO3 seems to improve hypotension and normalize QRS duration rapidly in most patients treated, and improve mental status changes in almost one half. Serum alkalinization with NaHCO3, in conjunction with appropriate supportive care, seems to limit major morbidity and mortality effectively in patients with serious CA overdose.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Child; Child, Preschool; Drug Overdose; Electrocardiography; Female; Humans; Hypertonic Solutions; Hypotension; Infant; Male; Middle Aged; Retrospective Studies; Sodium Bicarbonate

The effect of drug-specific antibody Fab' fragment on desipramine (DMI) toxicity was studied in anesthetized rats to determine 1) whether DMI-induced hypotension can be reversed, and 2) whether the effect of this Fab' fragment can be enhanced by the concurrent administration of hypertonic NaHCO3. DMI (60 mg/kg) was administered i.p. to produce marked hypotension. Antitricyclic antidepressant (TCA) Fab' (molar Fab'/DMI ratio = 0.11) or control Fab' was administered 15 min later as a 10 min i.v. infusion. The mean arterial pressure was higher at the end of anti-TCA Fab' infusion than after control Fab' (58 +/- 8 vs. 17 +/- 7 mm Hg, P less than .001). In a second protocol, DMI (30 mg/kg) was administered to prolong QRS duration. Anti-TCA Fab' alone (molar Fab'/DMI ratio = 0.09) and NaHCO3 alone both reduced QRS prolongation compared to control treatment, and combined therapy was more effective than either one alone. In both protocols, anti-TCA Fab' markedly increased the total DMI concentration and the bound fraction of DMI in serum, but did not alter the unbound DMI concentration. In the low DMI dose protocol, anti-TCA Fab' also reduced the cardiac DMI concentration. Concurrent treatment with anti-TCA Fab' and NaHCO3 substantially increased urinary DMI and anti-TCA Fab' excretion compared to treatment with anti-TCA Fab' alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bicarbonates; Desipramine; Drug Synergism; Electrocardiography; Hypotension; Immunoglobulin Fab Fragments; Male; Rats; Sodium; Sodium Bicarbonate

Topics: Bicarbonates; Cardiac Output, Low; Dialysis; Dialysis Solutions; Heart Rate; Humans; Hypotension; Sodium; Sodium Bicarbonate; Sympathetic Nervous System; Vascular Resistance

Cyclic antidepressant overdose is a major cause of drug overdose deaths and morbidity in the United States. The cyclic antidepressants are prescribed widely by primary care physicians and psychiatrists, and accidental overdose in children is not uncommon. Children have exhibited toxic effects with relatively small amounts of cyclic antidepressants. The management of cyclic antidepressant overdose is difficult because of the complex effects on the cardiovascular and nervous systems. The pertinent pharmacology of cyclic antidepressants in therapeutic amounts and in overdose is reviewed in this article. The clinical manifestations of cyclic antidepressant overdose are described. A protocol for effective management of cyclic antidepressant overdose in children is proposed.

Topics: Absorption; Acetylcholine; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Autonomic Nervous System; Bicarbonates; Child; Child, Preschool; Female; Heart Conduction System; Humans; Hypotension; Infant; Ipecac; Male; Norepinephrine; Phenytoin; Physostigmine; Seizures; Sodium; Sodium Bicarbonate; Tissue Distribution

The biofiltration with bicarbonate as dialysate buffer (BiBF) was used in 10 patients on RDT: the patients were treated for 10 months on standard BF and for 10 months on BiBF. The amount of fluid infused varied between 3 and 5 liters and Na-bicarbonate (100 mEq/h) was infused during BF. The dialytic protocol was 3 hours every other day. Cardiovascular stability, waste molecules and acid-base balance were investigated. No differences in vascular stability and no significant changes in the waste-molecules concentrations were found. Both protocols correct the metabolic acidosis; however, in standard BF 50% of patients showed acute hypocapnia at the end of dialysis.

Topics: Acid-Base Equilibrium; Acidosis; Bicarbonates; Blood; Buffers; Carbon Dioxide; Humans; Hypotension; Renal Dialysis; Sodium; Sodium Bicarbonate; Sodium Chloride; Ultrafiltration

Alkalinization of the blood by administration of sodium bicarbonate or hyperventilation is widely recommended for treatment of cardiac toxicity due to tricyclic antidepressant overdose, yet its efficacy and mechanism of action are poorly defined. We studied the effects and possible mechanism of action of 1 M NaHCO3 on desipramine (DMI) toxicity in anesthetized, paralyzed rats. Administration of DMI (45 mg/kg i.p.) produced a mean increase in QRS duration of 142% and a mean decrease in mean arterial pressure of 46%. Treatments were administered i.v. 35 min after DMI and their effects were assessed 10 min later. NaHCO3 (1 M) at doses of 3 and 6 mEq/kg decreased mean QRS duration 15 +/- 5 and 24 +/- 6%, respectively (mean +/- S.D.) and was superior to no treatment (P less than .01). NaCl (1 M) was as effective as NaHCO3 in decreasing QRS duration, as was 1 M NaHCO3 supplemented with 48 mM KCl. Respiratory alkalosis and 10% mannitol did not decrease QRS duration. NaHCO3, NaCl and NaHCO3/KCl all produced comparable increases in mean arterial blood pressure. Respiratory alkalosis and mannitol did not increase mean arterial pressure, but did prevent the decline seen in control animals. Acidosis produced by ventilation with 10% CO2 exacerbated QRS prolongation due to DMI. In acidotic animals, NaHCO3 and NaCl were equally effective in reversing QRS prolongation and hypotension. Correction of respiratory acidosis by discontinuation of inhaled CO2 did not improve QRS duration or mean arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis, Respiratory; Animals; Bicarbonates; Blood Pressure; Desipramine; Electrocardiography; Heart; Hypotension; Male; Mannitol; Potassium; Rats; Rats, Inbred Strains; Sodium; Sodium Bicarbonate; Sodium Chloride; Time Factors

Hemodialysis was performed in 12 patients for 2 weeks each utilizing acetate dialysate containing 134 mEq/L sodium and dialysate containing 143 mEq/L sodium, achieved by the addition of sodium chloride or sodium bicarbonate to the acetate dialysate. Intradialytic morbidity was lower, dialysis hypoxemia less marked, and predialysis blood pH higher with the bicarbonate-than with the chloride-added dialysate. The long-term use of sodium bicarbonate-added dialysate in three patients was safe. Dialysate pH adjustment was not required. These findings suggest that the addition of sodium bicarbonate (50-75 g) to acetate dialysate may be preferred to sodium chloride for increasing dialysate sodium in selected patients.

Topics: Aged; Bicarbonates; Blood Gas Analysis; Blood Pressure; Body Weight; Female; Humans; Hypotension; Long-Term Care; Male; Middle Aged; Muscle Cramp; Osmolar Concentration; Renal Dialysis; Sodium; Sodium Bicarbonate; Sodium Chloride; Solutions

Six patients with frequent episodes of symptomatic hypotension during acetate dialysis were treated with bicarbonate dialysis. In all patients blood pressure, heart rate, and arterial acid-base values were measured every 30 minutes during each of the five treatments with acetate dialysis and bicarbonate dialysis. Hemodynamic parameters were measured invasively in all patients during bicarbonate dialysis and in three of them also during acetate dialysis. Additionally, continuous long-time monitoring with electroencephalography was performed during acetate dialysis and bicarbonate dialysis. During acetate dialysis the patients showed a frequent onset of sudden hypotension and arrhythmia with concomitant symptoms of the so-called disequilibrium syndrome, whereas these symptoms were nonexistent in the same patients during bicarbonate dialysis.

Topics: Acetates; Acetic Acid; Bicarbonates; Blood Pressure; Body Weight; Electroencephalography; Heart Rate; Humans; Hypotension; Renal Dialysis; Sodium Bicarbonate; Vascular Resistance

Topics: Adult; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Bicarbonates; Female; Humans; Hypotension; Sodium Bicarbonate

Enuresis is a common problem often treated effectively with imipramine hydrochloride. The usefulness of this therapy carries with it, however, the risk of accidental overdose by younger siblings of these enuretic patients. Traditional support measures are effective in the treatment of the mild to moderate overdose, while separate symptomatic treatment of seizures and cardiac arrhythmias is possible as outlined herein. Physostigmine offers a single alternate treatment which is effective in the full panorama of life-threatening manifestations of an imipramine overdose.

Topics: Adult; Arrhythmias, Cardiac; Bicarbonates; Child; Child, Preschool; Coma; Diazepam; Drug Administration Schedule; Enuresis; Humans; Hypotension; Imipramine; Phenobarbital; Physostigmine; Seizures; Sodium Bicarbonate

Topics: Acetates; Bicarbonates; Buffers; Humans; Hyperlipidemias; Hypotension; Renal Dialysis; Sodium Bicarbonate

Topics: Acid-Base Equilibrium; Animals; Bicarbonates; Blood Volume; Dogs; Hyperbaric Oxygenation; Hypotension; Research; Shock; Shock, Hemorrhagic; Sodium Bicarbonate; Vascular Resistance

Topics: Acidosis; Bicarbonates; Blood Volume; Child; Drug Therapy; Femur; Humans; Hypotension; Infusions, Parenteral; Osteomyelitis; Resuscitation; Sepsis; Shock, Septic; Sodium Bicarbonate; Staphylococcal Infections