Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam

Zar, Tausif; Yusufzai, Irfan; Sullivan, Anna; Graeber, Charles

doi:10.1038/ncpneph0573

Cited by 35 publications

(17 citation statements)

References 19 publications

(36 reference statements)

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“…Propylene glycol toxicity is well described after prolonged dosing of infusions, especially in subjects with renal failure (3). Our subject developed a severe lactic acidosis from propylene glycol toxicity after a 10-hour infusion of 1.2 g. His serum propylene glycol concentration was among the highest ever reported, and his lactic acidosis was temporally related to his propylene glycol overdose.…”

Section: Discussionmentioning

confidence: 99%

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Severe Lactic Acidosis After an Iatrogenic Propylene Glycol Overdose

Zosel¹,

Egelhoff²,

Heard³

2010

Pharmacotherapy

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Propylene glycol is a diluent found in many intravenous and oral drugs, including phenytoin, diazepam, and lorazepam. Propylene glycol is eliminated from the body by oxidation through alcohol dehydrogenase to form lactic acid. Under normal conditions, the body converts lactate to pyruvate and metabolizes pyruvate through the Krebs cycle. Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain propylene glycol as a diluent. We describe a 50‐year‐old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic‐clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak propylene glycol level was 659 mg/dl, pH 6.9, serum bicarbonate level 5 mEq/L, and lactate level 18.6 mmol/L. Fomepizole was started the next day and was continued until hospital day 3. Continuous renal replacement therapy was started and then replaced with continuous venovenous hemofiltration (CVVH) for the remainder of the hospital stay. The patient's acidosis resolved by day 3, when his propylene glycol level had decreased to 45 mg/dl. Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died. Although the patient's outcome was death, his lactic acidosis was treated successfully with fomepizole and CVVH. Clinicians should be aware that an iatrogenic overdose of lorazepam may result in severe propylene glycol toxicity, which may be treated with fomepizole and CVVH. Key Words: propylene glycol, lorazepam, iatrogenic overdose, severe lactic acidosis, critical care, fomepizole.

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Section: Discussionmentioning

confidence: 99%

“…Our patient responded to fomepizole and hemodialysis, the standard treatments for toxic alcohol poisoning. Previous reports described the use of fomepizole for propylene glycol poisoning following prolonged infusion (3, 4). Fomepizole acts by inhibiting alcohol dehydrogenase, the first step in metabolism of propylene glycol.…”

Section: Discussionmentioning

confidence: 99%

Severe Lactic Acidosis After an Iatrogenic Propylene Glycol Overdose

Zosel¹,

Egelhoff²,

Heard³

2010

Pharmacotherapy

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“…Overall, one patient had a propylene glycol level of 58 mg/dl with no associated renal failure (Bledsoe and Kramer, 2008). It has been suggested that propylene glycol decreases renal clearance by saturating the proximal tubule [Speth et al 1987;Zar et al 2007]. A propylene glycol level was available only in one patient, but four other patients required hemodialysis for acute renal failure with metabolic abnormalities or volume overload.…”

Section: Discussionmentioning

confidence: 99%

Observed medical and surgical complications of prolonged barbiturate coma for refractory status epilepticus

Newey

Wisco

Nattanmai

et al. 2016

Therapeutic Advances in Drug Safety

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Background: Refractory status epilepticus is often treated with third-line therapy, such as pentobarbital coma. However, its use is limited by side effects. Recognizing and preventing major and minor adverse effects of prolonged pentobarbital coma may increase good outcomes. This study retrospectively reviewed direct and indirect medical and surgical pentobarbital coma. Methods: Retrospective chart review of all patients with refractory status epilepticus treated with pentobarbital over a 1 year period at a large tertiary care center. We collected baseline data, EEG data, and complications that were observed. Results: Overall, nine patients [median age 46.4 (IQR 21.7, 75.5) years] were induced with pentobarbital coma median 11 (IQR 3, 33) days after seizure onset for a median of 9 (IQR 3.5, 45.4) days. A total of four to eight concurrent antiepileptics were tried prior to the pentobarbital coma. Phenobarbital, due to recurrence of seizures on weaning pentobarbital coma, was required in seven patients. Observed complications included peripheral neuropathy (77.8%), cerebral atrophy (33.3%), volume overload (44.4%), renal/metabolic (77.8%), gastrointestinal (66.6%), endocrine (55.6%), cardiac/hemodynamic/vascular (77.8%), respiratory (100%), and infectious (77.8%). The number of complications trended with duration of induced coma but was nonsignificant. Median ICU length of stay was 40 (IQR 28, 97.5) days. Overall, five patients were able to follow commands after a median 37 (IQR 25.5, 90) days from coma onset. There were eight patients that were discharged from hospital with three remaining in a prolonged unresponsive state. There was one patient that died prior to discharge. Conclusions: This study highlights the high morbidity in patients with refractory status epilepticus requiring pentobarbital coma. Anticipating and addressing the indirect and direct complications in prolonged pentobarbital coma may improve survival and functional outcomes in patients with refractory status epilepticus.

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“…Acute phase proteins such as CRP [2],[3] and cytokines [4] are elevated markedly in association with infection and inflammation. During this process, local acidosis occurs due to massive infiltration of neutrophils and macrophages [5] to the site of infection, which subsequently, activates the respiratory burst [6],[7] in many infection-inflammation related diseases such as trauma-induced infection [8], acute renal failure [9], and intra-abdominal infection [10]. These pathological conditions can decrease the pH to as low as 5.5–7.0 [11].…”

Section: Introductionmentioning

confidence: 99%

Local Inflammation Induces Complement Crosstalk Which Amplifies the Antimicrobial Response

et al. 2009

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By eliciting inflammatory responses, the human immunosurveillance system notably combats invading pathogens, during which acute phase proteins (CRP and cytokines) are elevated markedly. However, the Pseudomonas aeruginosa is a persistent opportunistic pathogen prevalent at the site of local inflammation, and its acquisition of multiple antibiotic-resistance factors poses grave challenges to patient healthcare management. Using blood samples from infected patients, we demonstrate that P. aeruginosa is effectively killed in the plasma under defined local infection-inflammation condition, where slight acidosis and reduced calcium levels (pH 6.5, 2 mM calcium) typically prevail. We showed that this powerful antimicrobial activity is provoked by crosstalk between two plasma proteins; CRP∶L-ficolin interaction led to communication between the complement classical and lectin pathways from which two amplification events emerged. Assays for C4 deposition, phagocytosis, and protein competition consistently proved the functional significance of the amplification pathways in boosting complement-mediated antimicrobial activity. The infection-inflammation condition induced a 100-fold increase in CRP∶L-ficolin interaction in a pH- and calcium-sensitive manner. We conclude that the infection-induced local inflammatory conditions trigger a strong interaction between CRP∶L-ficolin, eliciting complement-amplification pathways which are autonomous and which co-exist with and reinforce the classical and lectin pathways. Our findings provide new insights into the host immune response to P. aeruginosa infection under pathological conditions and the potential development of new therapeutic strategies against bacterial infection.

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Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam

Abstract: Discontinuation of lorazepam infusion, administration of fomepizole, hemodialysis for five consecutive days, hemodynamic support, and follow-up of serum osmolality as a measure of propylene glycol decay.

Cited by 35 publications

References 19 publications

Severe Lactic Acidosis After an Iatrogenic Propylene Glycol Overdose

Severe Lactic Acidosis After an Iatrogenic Propylene Glycol Overdose

Observed medical and surgical complications of prolonged barbiturate coma for refractory status epilepticus

Local Inflammation Induces Complement Crosstalk Which Amplifies the Antimicrobial Response

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