Massive Overdose Research Articles

A Review of Emergency Cardiopulmonary Bypass for Severe Poisoning by Cardiotoxic Drugs

Cardiovascular collapse remains a leading cause of death in severe acute drug intoxication. Commonly prescribed medications such as antidysrhythmics, calcium channel antagonists, and beta adrenergic receptor antagonists can cause refractory cardiovascular collapse in massive overdose. Emergency cardiopulmonary bypass (ECPB), a modality originating in cardiac surgery, is a rescue technique that has been successfully implemented in the treatment of refractory cardiogenic shock and cardiac arrest unresponsive to traditional medical interventions. More recently a growing number of animal studies, case reports, and case series have documented its use in refractory hemodynamic collapse in poisoned patients. This article will review current ECPB techniques and explore its growing role in the treatment of severely hemodynamically compromised poisoned patients.

Positive Outcome After Intentional Overdose of Dabigatran

Dabigatran (Pradaxa™), an orally active direct thrombin inhibitor, was approved by the United States Food and Drug Administration for the prevention of stroke in patients with atrial fibrillation in October 2010. Life-threatening consequences from dabigatran therapy include hemorrhage and bleeding complications, but they typically occur after renal impairment. We describe the first case report of intentional, acute overdose with dabigatran. A 57-year-old woman with a medical history of depression and atrial fibrillation presented to the emergency department after ingesting 11.25g of dabigatran in a suicide attempt. Despite an ecchymosis indicative of prior trauma, there was no evidence of acute bleeding. After receiving gastric lavage and activated charcoal therapy in the emergency department, she was admitted to the ICU. On presentation, dabigatran blood levels measured 970ng/mL and thrombin clot times measured above the testable limits (>120s) until 52h post-arrival. The remainder of her clinical course was uncomplicated, and the patient was transferred to an inpatient psychiatric unit for depression follow-up. This case shows the clinical course of a patient with an acute, massive dabigatran overdose with no significant clinical consequences. Currently, there is no ideal method to monitor anticoagulation levels; there is no pharmacologic reversal method, and hemodialysis is an undesirable treatment option.

Methadone Toxicity and Possible Induction and Enhanced Elimination in a Premature Neonate

Reports describing methadone overdose in adult and pediatric patient populations are not uncommon. Reports in the preterm neonate patient population, however, are infrequent even though the utilization of methadone in that population continues to increase. Significant age-related pharmacokinetic differences complicate the management of methadone overdose in neonates, and literature involving methadone toxicokinetics and toxicodynamics in pediatric and neonate populations is largely limited. The clinical course and pharmacologic data of a massive methadone overdose in a 20-day-old male neonate is described, and a contemporary review of developmental pharmacology is presented. As clinicians continue to use methadone in neonates, they should be aware of the many significant peculiarities regarding its toxicology and pharmacology in that patient population.

Stress ulcer prophylaxis in critically ill poisoned patients

Letter to the editor Management of critically ill patients in the intensive care unit (ICU) is an important issue in medicine [1,2]. These patients may have clinically important bleeding, which is associated with an increased mortality rate. Mechanical ventilation may also increase the risk of bleeding in the upper gastrointestinal system. Sucralfate, histamine-2receptor antagonists, and proton pumps inhibitors (PPIs) are widely used for stress ulcer prophylaxis in critically ill adults [3]. Available data shows that PPIs are safe and efficacious for increasing intragastric pH in critically ill patients [4]. Since the superiority of the PPIs over histamine-2-receptor antagonists or sucralfate is not yet proved, they should only be used as an alternative to these agents. Poisoned patients may need to be admitted in ICU because of their critical condition. Poisoning with fatal agents such as aluminum phosphide, paraquat, organophosphate, or massive pharmaceutical drug overdoses usually needs ICU care and sometimes mechanical ventilation [5,6]. A question is therefore arisen: which of these agents is better to be used for ulcer prophylaxis in poisoned patients? Affection of the cytochrome P450 (CYP) by toxins or pharmaceutical drugs is an important point in answering this question. Generally, most of the toxicants have a liver metabolism [7]. The number of the known P450 enzyme inducers or inhibitors exceeds 1000, but P450 3A4 is the most frequent CYP in the human liver and is known to metabolize the majority of drugs whose biotransformation is known [8]. So, inhibition or induction of CYP may increase or decrease the final metabolites of the toxicants and may have a value in the treatment of poisoned patients in the ICU.

Hypoglycaemia: A little known effect of Venlafaxine overdose

We report the case of a 39-year-old woman who presented with serotonin syndrome and hypoglycaemia likely due to intoxication with a very high dose of venlafaxine. This case of venlafaxine-associated hypoglycaemia was treated first by glucose perfusion, but despite large doses, hypoglycaemia recurred. Blood glucose normalized after injection of octreotide, eliminating the need for hypertonic glucose. Octreotide has been shown to decrease glucose requirements and the number of hypoglycaemic episodes in patients with sulfonylurea-induced hypoglycaemia but, to our knowledge, its ability to resolve hypoglycaemic episodes due to massive venlafaxine overdose has not yet been described.

Treatment of Ivermectin Overdose in a Miniature Shetland Pony Using Intravenous Administration of a Lipid Emulsion

An 11-month-old miniature Shetland Pony colt weighing 26 kg was presented to the University of Zurich Equine Hospital for evaluation of acute onset of generalized seizures, followed by unconsciousness and recumbency, 34 hours after a massive (>25-fold) overdose of deworming paste (140 mg ivermectin and 1.05 g praziquantel). Instead of the labeled quantities of 0.2 mg ivermectin/kg and 1.5 mg praziquantel/kg, the foal had received the entire tube, equivalent to 5.4 mg ivermectin/kg and 40.4 mg praziquantel/kg. At presentation, the colt was in a stuporous condition but responded to pain stimuli including jugular venous catheter placement. Heart rate was 26/min, respiratory rate was 20/min, and rectal temperature was 34.5°C (94.1°F). The peripheral pulses were very weak and not detectable by palpation at all superficial arteries. Both jugular veins were poorly filled and capillary refill time was prolonged at approximately 3 seconds. The distal limbs and ears were cold to the touch. Palpebral and pupillary reflexes as well as menace responses were absent. In contrast, the corneal reflex was preserved and both eyes showed spontaneous horizontal nystagmus. Muscular tone of the tongue was decreased, whereas the anal reflex appeared normal. The clinical signs were most consistent with ivermectin intoxication. Ivermectin overdoses trigger severe neurologic signs by opening c-aminobutyric acid (GABA)-gated chloride channels, which in turn causes membrane hyperpolarization and blockade of neuronal impulses. In adult horses, no signs of intoxication are observed up to an ivermectin dosage of 1.8 mg/kg, whereas ingestion of 2 mg/kg has been shown to cause lethargy, ataxia, and visual impairment. The praziquantel overdose was considered less relevant in this foal, because praziquantel has a wide margin of safety, and the present exposure would result in only mild neurological and gastrointestinal signs. Analyses of blood samples at admission identified a low blood glucose concentration (3.4 mmol/L; normal, 3.6–6.1 mmol/L), normal plasma protein concentration (70 g/L; normal, 57–80 g/L) with low albumin (11 g/L; normal, 22–37 g/L) and increased globulin concentrations (59 g/L; normal, 27–50 g/L), a total bilirubin concentration of 9 lmol/L (normal, 9 –39 lmol/L), increased c-glutamyl transferase activity (GGT, 53 IU/L; normal, 5–24 IU/L), and low total calcium concentration (2.40 mmol/L; normal, 2.88– 3.55 mmol/L). Blood urea nitrogen and creatinine concentrations, as well as plasma sodium, potassium, and chloride concentrations, were within reference ranges. The blood lactate concentration was 2.3 mmol/ L (normal, <3 mmol/L). A CBC disclosed normocytic, normochromic anemia (hematocrit, 19.3%; normal, 30–42%; hemoglobin concentration, 7.0 g/dL; normal, 10.8–14.9 g/dL) with increased white blood cell count (WBC, 11.2 9 10/lL; normal, 4.7–8.2 9 10/lL). Treatment was initiated with warmed lactated Ringer’s solution (LRS) supplemented with glucose to a concentration of 2.5%, administered through a jugular venous catheter at a rate of 60 mL/kg/h. After 10 minutes, the blood glucose concentration had reached 8.3 mmol/L and treatment was continued with LRS without glucose at the same rate. After 1 hour, the fluid was changed to a maintenance crystalloid solution containing 1.5% glucose and the infusion rate was decreased to 4 mL/kg/h. By that time, peripheral pulse quality, jugular vein filling, and capillary refill time had improved, and the patient urinated. The colt was placed under a heat lamp, on a forced-air heating From the Equine Department, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland (Bruenisholz, Schwarzwald); the Institute of Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland (Kupper, Muentener, Naegeli); and the Institute of Forensic Medicine, Faculty of Medicine, University of Zurich, Zurich, Switzerland (Dally, Kraemer). The analytical methods described herein were previously presented as a research abstract. Dally AM, Kupper JR, Bruenisholz H, et al. Determination of ivermectin in plasma of a mini Shetland Pony after poisoning using LC-MS/MS – effectiveness of intravenous lipid therapy. 12th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology, Stuttgart, Germany, October 2–6, 2011. Corresponding authors: H. Naegeli, Prof. Dr. med. vet., Institute of Pharmacology and Toxicology; and C.C. Schwarzwald, PD Dr. med. vet., PhD, Dipl. ACVIM & ECEIM, Equine Department, Vetsuisse Faculty, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland; e-mails: naegelih@vetpharm.uzh.ch and cschwarzwald@ vetclinics.uzh.ch. Submitted October 11, 2011; Revised November 4, 2011; Accepted November 29, 2011. Copyright © 2012 by the American College of Veterinary Internal Medicine 10.1111/j.1939-1676.2011.00865.x Abbreviations:

Baclofen overdose mimicking brain death

Context. Brain death guidelines should be used with caution in patients with drug intoxication. It is often suggested that physicians use five half-lives of a drug when observing a patient with an overdose. We report two cases of baclofen intoxication where brain death was entertained as an explanation for prolonged coma, with arousal seen days later, suggesting that routine use of a 5-half-life observation period is insufficient with baclofen intoxication. Case presentation. A 40-year-old woman was found unresponsive by her family. Baclofen was found to be the responsible overdose. The patient had absent brain stem reflexes and was intubated and in the ICU for several days. Although EEG and Apnea test were inconclusive, the patient was thought to be brain dead and organ procurement was arranged. On hospital day 5, the patient started having purposeful movements. The patient had progressive arousal and was eventually transferred without neurologic sequelae to psychiatry. The second patient also had a massive baclofen overdose, had absence of almost all brain stem reflexes and was also intubated and in the ICU. Brain death was felt to be imminent, but the patient began to awake on hospital day 7. Discussion. Our two cases suggest that baclofen intoxication may result in very prolonged and profound coma and may, in fact, mimic brain death. Conclusion. The determination of brain death in the comatose overdose patient must proceed with caution. An adequate period of time to allow drug clearance must be allowed.

Massive Levemir (Long-Acting) Insulin Overdose: Case Report

A 52-year-old insulin-dependant diabetic man presented to the Emergency Department 2 hours after a deliberate massive overdose of 2100 units of long-acting Levemir insulin and a large quantity of whisky. On initial assessment, his GCS was 3/15 and his capillary blood sugar was 2.6 mmol/L. The patient was given a 50 ml bolus of 50% dextrose, followed by intravenous infusions of both 5% and 10% dextrose. Despite the continuous infusions, he experienced 4 symptomatic hypoglycaemic episodes in the first 12 hours after admission. These were managed with oral glucose, IM glucagon, and further dextrose boluses. Blood electrolytes and pH were monitored throughout. Insulin overdoses are relatively common and often occur with an excess of other drugs or alcohol which can enhance its action. Overdoses can result in persistent hypoglycaemia, liver enzyme derangement, electrolyte abnormalities, and neurological damage. Overall mortality is 2.7% with prognosis poorest in patients who are admitted with decreased Glasgow Coma scale (GCS) 12 hours after overdose.

Insulin glargine overdose

Insulin glargine is a long acting novel recombinant human insulin analogue indicated to improve glycemic control, in adults and children with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. The time course of action of insulins including insulin glargine may vary between individuals and/or within the same individual. Insulin glargine is given as a 24-h dosing regimen and has no documented half-life or peak effect. Hypoglycemia is the most common adverse effect of insulin, including insulin glargine. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. We present a case of a 76-year-old male insulin-dependent diabetic patient with refractory hypoglycemia secondary to an intentional overdose of insulin glargine. We would like to highlight the necessity of prolonging IV glucose infusion, for a much longer period than expected from pharmacokinetic properties of these insulin analogues after intentional massive overdose.

Chemical Necrotising Fasciitis Secondary to Self-Injection of Permethrin Insecticide

We report a 65-year-old male with chemical necrotising fasciitis after self-injection of permethrin insecticide. The patient also developed persistent hypoglycemia secondary to massive insulin overdose. There was no evidence of systemic toxicities from the insecticide poisoning. Multiple debridement and skin grafting were performed over his right forearm due to extensive tissue damage. He eventually recovered with impairment of his right hand function. The clinical features and the management of this uncommon route of insecticide poisoning are discussed. (Hong Kong j.emerg.med. 2011;18:441-445)

Severe sodium channel blockade and cardiovascular collapse due to a massive Lamotrigine overdose

Background. Cardiac arrest due to lamotrigine (LTG) has been reported after co-ingestion with bupropion, but severe sodium channel blockade in the absence of other toxins has not been described. We report a case of cardiac arrest and status epilepticus following a massive LTG overdose. Case Report. A 48 year-old female was brought to the ED with seizure-like activity subsequent to ingesting 7.5 g of LTG. Vital signs were HR 131, BP 107/68, T 99.4°F, RR 16. She was intubated in the ED for a low GCS. Initial ECG demonstrated a narrow-complex normal sinus rhythm, and her labs were unremarkable. Three hours after intubation she developed status epilepticus, and a pulseless wide-complex tachycardia. She was aggressively resuscitated during which time pulses were periodically reestablished, but lost each time seizures recurred. She was not stabilized until the convulsions were terminated with vecuronium. Her post-resuscitation ECG demonstrated a junctional tachycardia with a 3 mm R-wave in aVR. The LTG level was 74.7 mcg/ml (therapeutic: 3–14 mcg/ml). Comprehensive LC-MS/MS drug screen was negative for all screened compounds. Discussion. This is the first report of cardiovascular collapse due to LTG with the highest drug concentration to date. Conclusion. The degree of neurologic and cardiovascular toxicity seen in this case are novel and illustrate the potential for severe sodium channel blockade after massive LTG poisonings. Drug levels are not clinically relevant in the acute setting due to the time delay in obtaining results, and recurrent seizure activity may be the only clinical finding that precedes severe cardiac toxicity.

Reversible Carbamazapine Encephalopathy With Frontal Intermittent Rhythmic Delta Activity

Reversible Carbamazapine Encephalopathy With Frontal Intermittent Rhythmic Delta Activity

Massive Insulin Overdose Managed by Monitoring Daily Insulin Levels

We present a case of a significant insulin overdose that was managed by monitoring daily plasma insulin levels. A 39-year-old male with poorly controlled diabetes mellitus presented to the Emergency Department via emergency medical services after an attempted suicide by insulin overdose. In the attempted suicide, he injected 800 U of insulin lispro and 3800 U of insulin glargine subcutaneously over several parts of his abdomen. The patient was conscious upon arrival to the emergency department. His vital parameters were within normal range. The abdominal examination, in particular, was nonfocal and showed no evidence of hematomas. He was awake, alert, conversant, tearful, and without any focal deficits. An infusion of 10% dextrose was begun at 100 mL/h with hourly blood glucose (BG) checks. The patient was transferred to the intensive care unit where his BG began to decrease and fluctuate between 50 and 80 mg/dL, and the rate of 10% dextrose was increased to 200 mL/h where it was maintained for the next 48 hours. The initial plasma insulin level was found to be 3712.6 uU/mL (reference range 2.6-31.1 uU/mL). At 10 hours, this had decreased to 1582.1 uU/ml. On five occasions, supplemental dextrose was needed when the BG was <70 mg/dL. Thirty-four hours after admission, the plasma insulin level was 724.8 uU/mL. Fifty-eight hours after admission, the plasma insulin level was 321.2 uU/mL, and the 10% dextrose infusion was changed to 5% dextrose solution at 200 mL/h. The plasma insulin levels continued to fall daily to 112.7 uU/mL at 80 hours and to 30.4 uU/mL at 108 hours. He was transferred to an inpatient psychiatric facility 109 hours after initial presentation. Monitoring daily plasma insulin levels and adjusting treatment on a day-to-day basis in terms of basal glucose infusions provides fewer opportunities for episodic hypoglycemia. Furthermore, it was easier to predict daily glucose requirements and eventual medical clearance based on the plasma levels.

‘Where IT Meets IV’ Integrating Intravenous Infusion Devices With Hospital Information Systems

Tim Vanderveen is vice president of The Center for Safety and Clinical Excellence for CareFusion. E-mail: tim.vanderveen@ carefusion.com Since 2001, “smart” intravenous (IV) infusion pumps with dose-error-reduction software (DERS) have provided hospitals with critical safeguards against potentially fatal pump programming errors and a treasure trove of previously unavailable information on patient safety, IV practices, and quality of care. Nevertheless, IV infusion errors that result in harmful and even fatal adverse drug events (ADEs) are a continuing concern. In response to numerous safety and performance issues with IV infusion pumps, the Association for the Advancement of Medical Instrumentation (AAMI) joined with the Food and Drug Administration (FDA) to host a summit on infusion devices in October 2010. As described in the subsequent conference report, Infusing Patients Safely, a multidisciplinary steering committee was formed to lead a number of working groups in establishing priorities, developing guidelines, and identifying and sharing best practices to improve the safety of IV infusions. Although the agendas of the various working groups are still being developed, the steering committee has adopted a set of future vision statements to help guide it and the working groups in their efforts to make IV infusions safer. The vision boldly describes an attainable state and sets an aggressive national agenda to capitalize on the present opportunities, stating as its mission that “no patient will be harmed from a drug infusion.” The vision starts with establishing wireless connectivity between a hospital’s hundreds of infusion pumps and the hospital’s wireless network. Without this connectivity, other significant advances for improving infusion safety will be impossible to achieve. With this connectivity, an exciting new state of greatly improved safety, quality and productivity can be attained. This article is based on vendor experience in working with hospital partners to implement wireless connectivity for more than 300,000 infusion devices on wireless networks across hospitals of all sizes and levels of complexity. The benefits, challenges and opportunities of integrating infusion devices into hospitals’ health information technology (HIT) systems will be addressed, along with ways to meet the challenges. The potential impact of the continuing convergence of clinical engineering and information technology (IT) will also be covered.

Lipid rescue of massive verapamil overdose: a case report

IntroductionMassive intentional verapamil overdose is a toxic ingestion which can cause multiorgan system failure and has no currently known antidote.Case PresentationThe patient is a 41-year-old Caucasian woman who ingested 19.2 g of sustained release verapamil in a suicide attempt. Our patient became hypotensive requiring three high-dose vasopressors to maintain arterial pressure. She also developed acute respiratory failure, bradycardic ventricular rhythm necessitating continuous transvenous pacing, and anuric renal failure. Our patient was treated with intravenous calcium, bicarbonate, hyperinsulinemic euglycemic therapy and continuous venovenous hemodialysis without success. On the fourth day after hospital admission continuous intravenous lipid therapy was initiated. Within three hours of beginning lipid therapy, our patient's vasopressor requirement decreased by half. Within 24 hours, she was on minimal vasopressor support and regained an underlying junctional rhythm. After three days of lipid infusion, she no longer required inotropic agents to maintain blood pressure or pacing to maintain stable hemodynamics.ConclusionsIntravenous fat emulsion therapy may be an effective antidote for massive verapamil toxicity.

Image in toxicology: Pseudo-subarachnoid hemorrhage in a case of severe valproic acid poisoning

Pseudo-subarachnoid hemorrhage (PSAH) is a false-positive finding on cranial computed tomography (CT) in patients with cerebral edema. Its appearance on CT resembles subarachnoid hemorrhage despite the absence of subarachnoid blood. We report the finding of PSAH in a case of massive valproic acid overdose.

Massive Clonidine Overdose During Refill of an Implanted Drug Delivery Device for Intrathecal Analgesia: A Review of Inadvertent Soft-Tissue Injection During Implantable Drug Delivery Device Refills and Its Management

The study aims to highlight the potentially serious consequences of inadvertent soft-tissue injection of intrathecal drugs such as clonidine, during refills of implanted drug delivery devices, and to suggest strategies to reduce this complication. Case report and literature review were used. We report the case of a 51-year-old female with chronic arm pain who sustained a massive clonidine overdose (18,000 mcg) due to inadvertent soft-tissue injection during a refill of an implanted drug delivery device, resulting in rapid loss of consciousness and significant cardiovascular instability requiring urgent resuscitation, subsequent myocardial infarction, cardiac failure, and other significant complications. The risks of inadvertent soft-tissue injection of intrathecal drugs during implanted drug delivery device refills and management of such events is poorly documented in the literature. Inadvertent soft-tissue injection is possibly an underappreciated and underreported complication of intrathecal analgesia via an implanted drug delivery device. Under some circumstances, large doses of other intrathecal drugs such as bupivacaine, opioids, ziconotide, and baclofen may also be delivered by inadvertent soft-tissue injection with potentially life-threatening consequences. We recommend that practitioners, institutions, and professional bodies who manage patients with intrathecal analgesia via intrathecal drug delivery devices highlight and audit this complication and develop systems to manage it.

Acquired 5‐Oxoprolinuria (Pyroglutamic Acidaemia) as a Cause of Early High Anion Gap Metabolic Acidosis in Acute Massive Paracetamol Overdose

5‐oxoprolinuria is an uncommon and under‐recognised cause of early high anion gap metabolic acidosis after paracetamol overdose. We reported a 30‐year‐old Indian woman with history of chronic alcoholism who ingested 150 g crushed paracetamol tablets for suicide 14 hours before attendance to the A&amp;E Department. Initial arterial blood gas showed a high anion gap metabolic acidosis with respiratory compensation. Serum paracetamol level reached 5004 umol/L and a prolonged course of N‐acetylcysteine was given. She was complicated by hepatotoxicity and 5‐oxoprolinuria (with laboratory confirmation) which reverted after antidote administration. There were no neurological and hepatic sequelae. In case of massive overdose, pathways of drug metabolism are altered prior to the centrilobular hepatic necrosis. A metabolic intermediate of gamma‐glutamyl cycle, 5‐oxoproline, accumulates upon saturation of endogenous glutathione store. The specific antidote N‐acetylcysteine is the only definitive treatment. Prolonged course of antidote may be required in cases of massive overdose and treatment should be individualised. (Hong Kong j.emerg. med. 2011;18:264‐270)

Extra-corporeal life support for near-fatal multi-drug intoxication: a case report

IntroductionSevere mixed β-blocker and calcium channel blocker intoxication presents a significant risk for patient mortality. Although treatment is well-established, it sporadically fails to support the patient through massive overdoses, thus requiring non-conventional treatments. We report the use of extra-corporeal life support in a patient with refractory hemodynamic impairment due to multi-drug intoxication. Although sometimes used in clinical practice, extra-corporeal membrane oxygenation for intoxications has rarely been reported.Case presentationA 36-year-old Caucasian man presented to our hospital with refractory hypotension, severe cardiac insufficiency and multi-organ failure due to mixed intoxication with atenolol, nifedipine, Lacidipine and sertraline. Together with standard treatment, we performed extra-corporeal membrane oxygenation to overcome refractory cardiogenic shock and lead the patient to achieve a full recovery.ConclusionStandard of care for β-blocker and calcium channel blocker intoxication is well-defined and condensed into protocols of treatment. Although aimed at clearing the noxious agents from the patient's system, standard measures may fail to provide adequate hemodynamic support to allow recovery. In selected cases, extra-corporeal membrane oxygenation could be considered a bridge to drug clearance while preventing multi-organ failure due to profound shock.

Finding knizocytes in a peripheral blood smear

A 61-year-old female with unremarkable medical history and no evidence of chronic alcohol abuse presented with acute liver failure secondary to massive paracetamol overdose. Laboratory tests indicated: Hb 11.5 g/dL (reference value, RV ≥ 12), WBC 13.8 × 109/L (RV ≤ 10), platelets 45 × 109/L (RV ≥ 150), bilirubin 238 μmol/L (RV ≤ 25), GOT/ASAT 210 UI/L (VR < 30), GPT/ALAT 103 UI/L(RV < 40), alcaline phosphatase 212 UI/L, RV < 120), cholesterol 3.2 mmol/L (RV ≤ 3.9), and triglycerids 6.5 mmol/L (RV ≤1.7). The plasma did not show visible hemolysis. Blood smear (Image 1, May Grünwald Giemsa, ×1000) demonstrated numerous knizocytes in a background of moderate poïkilocytosis. Mosaic image of knizocytes (May-Grünwald-Giemsa 1000×). Knizocytes are triconcave RBCs with a “ridge,” a “bridge” separating the three concavities (in scanning electron micrograph), or a strip of hemoglobin crossing the clear central area (in standard staining). They are very rarely observed in routine practice even if their percentage was estimated once 0.6% ± 0.5 in healthy controls (min-max values: 0–2.5%) [1]. By contrast, they are regularly seen in newborns where they are considered as relatively young RBCs with impaired membrane deformability usually among stomatocytes, spherocytes, and erythrocytes with spicules and protrusions (echinocytes/acanthocytes) [2]. In adults, they are mainly observed in the context of anomalies of the cholesterol metabolism related to any acute liver dysfunction. As the RBCs morphology is influenced by the membrane lipid content and as RBCs exchange continuously lipids with plasma [3], change in circulating lipids levels associated with acute liver disease can alter the RBCs shape, in a delay shorter than their lifetime, as recently reported in this journal [4] or by others [5]. More chronically, knizocytes and/or target cells are observed in patients with familial lecithin/cholesterol acyltransferase deficiency, which induce a decrease in the membrane deformability and as a consequence a higher RBCs fragility [4, 6]. Knizocytes are also frequently observed in chronic liver diseases as chronic hepatitis or cirrhosis (alcoholic or postviral causes) where they can account for up to 15% of the red cells [7]. Alcohol abuse induce a variety of changes in the RBC morphology, including typically round macrocytes, stomatocytes but also knizocytes related to the presence of acetaldehyde-derived epitopes both on the cell membrane and inside the RBCs [8]. Although nonspecific, observation of knizocytes on a blood smear should prompt an assessment of liver function and lipid parameters.