Letter to the Editor
Use of continuous venovenous hemodiafiltration in a case of severe pentobarbital poisoning
Uso de hemodiafiltración venovenosa continua en un caso de intoxicación grave por pentobarbital
a Servicio de Medicina Intensiva, Hospital Universitario Son Llàtzer, Palma de Mallorca (Islas Baleares), Spain
b Unidad de Toxicología Clínica, Servicio de Análisis Clínicos, Hospital Universitario Son Espases, Palma de Mallorca (Islas Baleares), Spain
c Grupo de Investigación en Toxicología Clínica, Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma de Mallorca (Islas Baleares), Spain
d Departamento de Medicina, Facultad de Medicina, Universidad de las Islas Baleares, Palma de Mallorca (Islas Baleares), Spain
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T.C.: therapeutic concentration; CVVHDF: continuous venovenous haemodiafiltration.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pentobarbital is a short-acting sedative hypnotic barbiturate used both clinically, for the control of refractory intracranial hypertension in severe head injury, and widely in veterinary medicine, in anaesthesia and euthanasia procedures.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Cases of euthanasia or legal assisted suicide and so-called ‘suicide tourism’ have been described in the medical literature.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report a non-fatal case of a veterinarian who injected himself with a syringe filled with pentobarbital, with no data on the dose, who was treated with continuous venovenous haemodiafiltration (CVVHDF) with the aim of reducing the return time of brainstem reflexes and the duration of intubation. We present the results of serial monitoring of serum pentobarbital and dialysate effluent during the clinical course.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of a 50-year-old male, with a history of major depression and multiple self-harm attempts, under treatment with mirtazapine, pregabalin, sertraline and lorazepam. He was brought in by ambulance for coma secondary to drug poisoning with suicidal intent. He was found with a low level of consciousness, Glasgow Coma Scale of 7 points, by the out-of-hospital emergency service, together with a syringe of pentobarbital and signs of venipuncture, for which it was decided to transfer him to the intensive care unit. On arrival he had a GCS of 3, with hyporeflective miotic pupils, normal blood pressure (120/85<span class="elsevierStyleHsp" style=""></span>mmHg), sinus rhythm at 65<span class="elsevierStyleHsp" style=""></span>bpm, SpO<span class="elsevierStyleInf">2</span> 100% with non-rebreather mask, bradypnoea with 8 breaths per minute and hypothermia (35.0<span class="elsevierStyleHsp" style=""></span>°C). The patient was intubated and put on mechanical ventilation. The electrocardiogram showed a sinus rhythm at 65<span class="elsevierStyleHsp" style=""></span>bpm with QTc 430<span class="elsevierStyleHsp" style=""></span>ms, without significant arrhythmias. The blood test showed no abnormalities.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The case was classified as coma secondary to pentobarbital poisoning with suicidal intent, without ruling out multiple poisoning. Blood alcohol content was <0.1<span class="elsevierStyleHsp" style=""></span>g/L. Urine toxicological screening was positive for barbiturates and the presence of pentobarbital was confirmed by GC–MS, as well as mirtazapine, pregabalin, sertraline and lorazepam. On admission to intensive care, serum pentobarbital levels (GC–MS) were 17.12<span class="elsevierStyleHsp" style=""></span>μg/mL (therapeutic range: 1–10<span class="elsevierStyleHsp" style=""></span>μg/mL). The levels of the remaining drugs (HPLC–MS/MS) were in therapeutic or sub-therapeutic range: mirtazapine 16<span class="elsevierStyleHsp" style=""></span>ng/mL; pregabalin 3.1<span class="elsevierStyleHsp" style=""></span>μg/mL; sertraline 1<span class="elsevierStyleHsp" style=""></span>ng/mL; fluvoxamine 58<span class="elsevierStyleHsp" style=""></span>ng/mL and lorazepam 13<span class="elsevierStyleHsp" style=""></span>ng/mL. During the first 48<span class="elsevierStyleHsp" style=""></span>h no changes were observed on neurological examination. At 36<span class="elsevierStyleHsp" style=""></span>h after admission, CVVHDF was started; 24<span class="elsevierStyleHsp" style=""></span>h after initiation, myoclonus of presumed toxic-metabolic cause occurred, with progressive improvement in the level of consciousness, although with agitation that was difficult to control and required pharmacological treatment. A cranial CT scan showed no pathological findings. CVVHDF was discontinued 72<span class="elsevierStyleHsp" style=""></span>h after initiation with no worsening of the level of consciousness.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Monitoring of serum pentobarbital concentrations and dialysate effluent (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) showed a peak serum concentration of 29.0<span class="elsevierStyleHsp" style=""></span>μg/mL at 2.7<span class="elsevierStyleHsp" style=""></span>h after admission. The serum elimination half-lives (t1/2) pre-CVVHDF and post-CVVHDF were 91.2 and 24.8<span class="elsevierStyleHsp" style=""></span>h, respectively. The neurological progression was favourable, with progressive improvement of agitation, without motor focality or cognitive deficit. He was discharged after 12 days of hospital admission.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Pentobarbital levels are not widely available, so the clinical manifestations on the central nervous system, pulmonary and cardiovascular systems are the most important in assessing poisoning severity and recovery.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The pentobarbital concentration considered fatal is 30<span class="elsevierStyleHsp" style=""></span>μg/mL, very close to the maximum concentration observed in this patient.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In his management it was decided to initiate extracorporeal elimination techniques although their use is controversial in short-acting barbiturate poisoning.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,5</span></a> The pentobarbital concentrations obtained in the dialysate effluent allowed the assessment of the contribution of this technique in terms of accelerating clearance.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Short-acting barbiturates are more protein-bound and lipid-soluble than long-acting barbiturates; they are less susceptible to elimination by urinary alkalinisation and are metabolised almost exclusively in the liver. In addition, pentobarbital is an active metabolite of thiopental.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In our case, no thiopental was detected. Pentobarbital induces its own metabolism at therapeutic and toxic doses.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In the case reported, the CVVHDF procedure was associated with an improvement in the patient’s clinical condition and a rapid decrease in pentobarbital levels, without being able to rule out that this process was also accelerated due to autoinduction of hepatic metabolism.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0050" class="elsevierStylePara elsevierViewall">Informed written consent was obtained from the patient for publication of the article.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">The present research has not received any funding.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest in relation to this paper.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1004 "Ancho" => 1675 "Tamanyo" => 107034 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0170" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Monitoring of pentobarbital level in serum and dialysate effluent during continuous venovenous haemodiafiltration treatment.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">L.C.: lethal concentration; T.C.: therapeutic concentration; CVVHDF: continuous venovenous haemodiafiltration.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enhanced elimination in acute barbiturate poisoning — a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.M. 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