Carboxyhemoglobin half-life toxicokinetic profiles during and after normobaric oxygen therapy: On a swine model.

Investigations on acute carbon monoxide (CO) poisoning struggle to highlight a relevant discriminant criterion related to CO poisoning severity for predicting complications, such as delayed neurological syndromes. In this context, it remains difficult to demonstrate the superiority of one method of oxygen (O2) administration over others or to identify the optimal duration of normobaric 100% oxygen (NBO) treatment. Myoglobin, as hemoglobin, are a potential binding site for CO, which could be a source of extravascular CO storage that impacts the severity of CO poisoning. It is not possible in routine clinical practice to estimate this potential extravascular CO storage. Indirect means of doing so that are available in the first few hours of poisoning could include, for example, the carboxyhemoglobin half-life (COHbt1/2), which seems to be influenced itself by the level and duration of CO exposure affecting this store of CO within the body. However, before the elimination of CO can be assessed, the COHbt1/2 toxicokinetic model must be confirmed: research still debates whether this model mono- or bi-compartmental. The second indirect mean could be the assessment of a potential COHb rebound after COHb has returned to 5% and NBO treatment has stopped. Moreover, a COHb rebound could be considered to justify the duration of NBO treatment. On an experimental swine model exposed to moderate CO poisoning (940 ppm for ±118 min until COHb reached 30%), we first confirm that the COHb half-life follows a bi-compartmental model. Secondly, we observe for the first time a slight COHb rebound when COHb returns to 5% and oxygen therapy is stopped. On the basis of these two toxicokinetic characteristics in favor of extravascular CO storage, we recommend that COHbt1/2 is considered using the bi-compartmental model in future clinical studies that compare treatment effectiveness as a potential severity criterion to homogenize cohorts of the same severity. Moreover, from a general toxicokinetic point of view, we confirm that a treatment lasting less than 6 hours appears to be insufficient for treating moderate CO poisoning.

Long-term intensive care unit outbreak of carbapenemase-producing organisms associated with contaminated sink drains.

BACKGROUND: Between 2018 and 2022, a Belgian tertiary care hospital faced a growing issue with acquiring carbapenemase-producing organisms (CPO), mainly VIM-producing P. aeruginosa (PA-VIM) and NDM-producing Enterobacterales (CPE-NDM) among hospitalized patients in the adult intensive care unit (ICU). AIM: To investigate this ICU long-term CPO outbreak involving multiple species and a persistent environmental reservoir. METHODS: Active case finding, environmental sampling, whole-genome sequencing (WGS) analysis of patient and environmental strains, and implemented control strategies were described in this study. FINDINGS: From 2018 to 2022, 37 patients became colonized or infected with PA-VIM and/or CPE-NDM during their ICU stay. WGS confirmed the epidemiological link between clinical and environmental strains collected from the sink drains with clonal strain dissemination and horizontal gene transfer mediated by plasmid conjugation and/or transposon jumps. Environmental disinfection by quaternary ammonium-based disinfectant and replacement of contaminated equipment failed to eradicate environmental sources. Interestingly, efflux pump genes conferring resistance to quaternary ammonium compounds were widespread in the isolates. As removing sinks was not feasible, a combination of a foaming product degrading the biofilm and foaming disinfectant based on peracetic acid and hydrogen peroxide has been evaluated and has so far prevented recolonization of the proximal sink drain by CPO. CONCLUSION: The persistence in the hospital environment of antibiotic- and disinfectant-resistant bacteria with the ability to transfer mobile genetic elements poses a serious threat to ICU patients with a risk of shifting towards an endemicity scenario. Innovative strategies are needed to address persistent environmental reservoirs and prevent CPO transmission.

Refractory hypercapnia: a simplified technique for extracorporeal CO2 removal (ECCO2R) in the presence of therapeutic limitations.

Refractory hypercapnia with severe acidosis appeared in a 67-year-old man who presented with lung fibrosis and a left pneumothorax as delayed complications of bleomycin chemotherapy for advanced grade lymphoma. Due to failure of noninvasive ventilation using a high-flow nasal cannula oxygen system, the patient was mechanically ventilated with two ventilators at different settings, after intubation with a double-lumen tube. As he had a poor haematological prognosis, extracorporeal membranous oxygenation was not considered. To remove some amount of carbon dioxide, we used a simplified method based on a veno-venous hemofiltration circuit coupled to a paediatric oxygenator and an air/oxygen blender. The efficacy on carbon dioxide removal was modest, with a percentage of CO2 total extraction ranging from 10.5 to 20.4%, but the system was immediately available, well tolerated and not very expensive.

Locked-in syndrome as an unusual complication of acute otitis media.

BACKGROUND: A 32-year-old woman developed altered consciousness two days after initial symptoms of acute otitis media, with purulent discharge from the right ear. She was quadriplegic, with spontaneous eye opening, mild neck stiffness, and lacking vestibular-ocular reflexes. METHODOLOGY: Upon admission, the patient was subjected to brain computed tomography (CT), magnetic resonance imaging (MRI), and lumbar puncture. RESULTS: CT was consistent with pansinusitis, right middle ear otitis, mastoiditis, and sphenoiditis. No brainstem lesion was evident; brain MRI demonstrated ischemic and secondary hemorrhagic lesions in the pons and cerebral peduncles. The dura mater in the petroclival space was intensely inflamed, and likely responsible for reduced basilar arterial blood flow. Lumbar puncture yielded clear cerebrospinal fluid; gram stain examination was negative and culture remained sterile. Streptococcus pneumoniae and Haemophilus influenzae were cultured from the purulent ear discharge. CONCLUSION: The final diagnosis was locked-in syndrome consecutive to inflammatory changes compressing the basilar artery.

Reversible splenial lesion syndrome in cerebral malaria.

A 71-year-old Caucasian man living in Congo was investigated by serial magnetic resonance imaging (MRI) after having presented cerebral malaria due to Plasmodium falciparum. The clinical picture was characterized initially by coma and seizures. The patient developed multiple organ failure. There was, at 4 months follow-up only, a minimal neurological improvement consistent with minimally conscious state. The first cerebral MRI on day 17 showed a lesion of the splenium of corpus callosum with high signal intensity on DWI and FLAIR sequence and reduced ADC, and small cortical infarcts in the internal occipital regions. Follow-up MRI obtained 36 days later showed a complete resolution of splenial lesion, though without clinical improvement. Cerebral malaria should be added to the list of possible causes of reversible lesion of the splenium of corpus callosum.

Extreme Rhabdomyolysis, Acute Renal Failure, and Protracted Ileus in a Case of Legionella Pneumonia.

A 53-year-old man developed a Legionella pneumophila pneumonia complicated by rhabdomyolysis, acute kidney injury, and protracted ileus. Risk factors were smoking and chronic alcoholism, but the patient had no history of previous abdominal surgery. Hemodialysis was required for a period of 5 weeks with a full renal recovery. Pneumonia required respiratory support but for a limited period of 6 days. The protracted course of the ileus led to explorative laparotomy despite negative computed tomography findings. No cause of mechanical obstruction was found at surgery and common etiologies of intestinal obstruction were excluded. Parenteral nutrition was needed for a total of 4 weeks, before recovery of intestinal motility. This case illustrates the apparent discrepancy between the pulmonary symptoms and the extrapulmonary manifestations that could be seen as a consequence of an exaggerated immune response.

Non-heart-beating donor, 10-year experience in a Belgian transplant center.

All over the world, transplant teams are looking for ways to increase and improve the donor pool. Non-heart-beating donation may increase the number of donors, even if some technical, logistical, and emotional problems are still encountered. The results obtained by our team should stimulate other centers to implement this kind of donation in their hospitals. Herein we have described our experience with non-heart-beating donation.

Neuroinvasive Infection from O117:K52:H-Escherichia coli following Acute Pyelonephritis.

Spontaneous or nosocomial Escherichia coli meningitis remains rare in healthy adults but is still carrying a high mortality rate despite adapted antimicrobial treatment for susceptible strains. A 39-year-old woman was admitted to the hospital with severe subarachnoid haemorrhage complicated by acute hydrocephalus. On hospital day 10, she developed Streptococcus anginosus septicaemia and urinary tract infection due to a multisensitive strain of E. coli. This infection was successfully controlled by antimicrobial therapy. As a late complication in the neurosurgical ward (day 39), she developed fever, alteration of consciousness, and shock, leading to the diagnosis of bacterial meningitis. The culture of blood, cerebrospinal fluid, and urine grew positive for a multisensitive E. coli. The strain was identified as O117:K52:H, a serotype that was until now never associated with acute meningitis or brain abscesses. The source appeared to be the urinary tract with the demonstration of acute pyelonephritis. The patient died on day 94 from delayed complications of multiple brain abscesses.

Acute Bacterial Meningitis and Systemic Abscesses due to Streptococcus dysgalactiae subsp. equisimilis Infection.

Disseminated abscesses due to group G ß-hemolytic Streptococcus dysgalactiae were observed in a 57-year-old cirrhotic patient with the skin being the putative way of entry for the pathogen. S. dysgalactiae is a rare agent in human infections responsible for acute pyogenic meningitis. The mortality rate associated with S. dysgalactiae bacteraemia and meningitis may be as high as 50%, particularly in the presence of endocarditis or brain abscesses. In our patient, main sites of infections were meningitis and ventriculitis, spondylodiscitis, septic arthritis, and soft-tissue infections. In contrast, no endocarditis was evidenced. Cirrhosis-related immune suppression was considered as a pathophysiological cofactor for the condition. Fortunately, clinical status improved after long-term (3 months) antimicrobial therapy.

Non-heart-beating donor, renewal of an old procedure: a Belgian experience.

The shortage of donated organs has become a problem in transplantation throughout the world. Transplant teams are looking for other ways to increase and improve the donor pool. Non-heart-beating donation may be a source to increase the number of donors, even if some technical, logistical, and emotional problems are encountered. The results obtained by our team should stimulate other centers to implement this kind of donation in their hospitals. We describe our experience in the policy of non-heart-beating donation and encourage transplant centers to develop such a program.

Formate kinetics in methanol poisoning.

OBJECTIVE: The objective is to describe the kinetics of formate, the main toxic metabolite of methanol, in a series of consecutive patients treated in the same intensive care unit for severe methanol poisoning. METHODS: The charts of the patients admitted between 1987 and 2001 were reviewed. Inclusion criteria were: a history of deliberate methanol ingestion, with a blood methanol concentration greater than 20 mg/dL (6.2 mmol/L) or a high anion gap metabolic acidosis. Indications for hemodialysis were: blood methanol concentration >50 mg/dL (15.8 mmol/L), metabolic acidosis (bicarbonate <15 mmol/L, arterial pH <7.30), visual toxicity. Antidotal therapy included ethanol administration in 22 cases, and fomepizole in three cases. Serial blood measurements were obtained for pH, bicarbonate, methanol and formate. Endogenous and hemodialysis elimination half-lives were calculated as t1/2 =0.693/Ke. Fick principle was applied for hemodialysis clearance calculation. RESULTS: The records of 25 methanol poisoned patients were analysed. Among them, 18 patients had sufficient data to allow accurate determinations of formate kinetics. Formate half-life elimination during hemodialysis was 1.80+/-0.78 h, which was statistically different from the values observed before or in the absence of dialysis (6.04+/-3.26 h, P =0.004). The mean hemodialysis formate clearance rate calculated in eight cases was 176+/-43 mL/min. A rebound in plasma formate concentration was observed in three patients after the discontinuation of hemodialysis. CONCLUSIONS: In accordance with previous isolated case reports and in contrast with a recent case series, our data document that hemodiaysis is effective in reducing formate elimination half-life. The impact on clinical outcome is still debatable.

[Acute methanol intoxication: physiopathology, prognosis and treatment]. / Intoxication aiguë par le méthanol: physiopathologie, pronostic et traitement.

Acute methanol poisoning is still complicated by a poor vital or visual prognosis. The pathophysiology of methanol poisoning is not yet fully understood. It appears that the major toxic effects are related to the main metabolite of methanol, formic acid. The central nervous system and the visual pathway are the main targets of methanol poisoning. When irreversible brain lesions occur, the diagnosis of brain death can be made. Other organs, like the pancreas or the kidney, may also be damaged according to the severity of metabolic acidosis; however, the toxic manifestations are in this case mostly reversible. The historical treatment of methanol poisoning relies on ethanol administration. However, ethanol therapy has numerous side effects and a new antidote, fomepizole, that was previously approved for the treatment of ethylene glycol poisoning, appears effective, safe and easy to use. Hemodialysis remains effective for the removal of both methanol and formic acid.

Susac-like syndrome in a chronic cocaine abuser: could levamisole play a role?

INTRODUCTION: Toxic leukoencephalopathy is a possible but rare complication of chronic cocaine abuse. The role of adulterants, mainly levamisole, is still debated. CASE REPORT: We describe an atypical case of fatal leukoencephalopathy mimicking Susac syndrome in a 22-year-old man who was chronically abusing cannabis and cocaine. Exposure to levamisole as adulterant to cocaine was proven by hair analysis. Despite cessation of exposure to cocaine and aggressive immunosuppressive therapy, the patient remained in a minimally conscious state until death. DISCUSSION: Susac syndrome is a rare entity, and its etiology is not yet fully elucidated. The toxic etiologies have been poorly investigated to date. Further observations are required to determine if cocaine and/or adulterants might play a significant role.

Successful double lung transplantation with a graft obtained from a methanol-poisoned donor.

A 25-year-old woman developed "brain death" 48 h after acute methanol poisoning. After the elimination of methanol and the correction of metabolic disorders, organ donation was discussed. The lungs were transplanted into a 46-year-old woman suffering from cystic "emphysematous-like" lesions as a complication of lymphangioleiomyomatosis. The procedure was not complicated, and we have an uneventful follow-up of > 12 months. In addition to the lungs, the kidneys and the liver were also removed and transplanted with success.

Early complications and value of initial clinical and paraclinical observations in victims of smoke inhalation without burns.

OBJECTIVE: To evaluate the incidence of early pulmonary complications and the value of initial clinical signs and paraclinical investigations in victims of smoke inhalation not suffering from burns following structural fires. DESIGN: Retrospective chart review. SETTING: Thirteen-bed ICU. PATIENTS: Sixty-four victims of smoke inhalation following household fires were admitted to the ICU between January 1987 and December 1992. Exclusion criteria from the study were patients with cutaneous burns or multiple trauma or blast injury, and patients found in cardiac arrest. METHODS: Clinical, biological, and radiologic parameters were collected over a 5-day period. RESULTS: The mortality rate in relation to progressive respiratory failure was 3.1%. Mean ICU stay was 5.8 days (range, 1 to 33 days), and was longer in the patients presenting with soot deposits in the oropharynx (p = 0.02), dysphonia (D) (p = 0.05), or ronchi (R) (p = 0.0004) at the first examination, and in those having a positive sputum bacteriologic analysis (p = 0.003) or requiring parenteral bronchodilator agents for more than 24 h (p = 0.04). Thirty-five patients underwent mechanical ventilation (MV) for a mean of 101.2 h (range, 8 to 648 h). Mean MV duration was higher in the patients presenting initially with R (p = 0.003), high carbon monoxide (but not cyanide) levels (p = 0.02), or a positive bacteriologic sample (p = 0.0001). Positive bacteriologic sampling correlated with the presence of D (p = 0.02) or R (p = 0.04) and with immediate intubation (p = 0.0003). No correlation was found with chest radiograph. CONCLUSIONS: In this selected series of fire victims without cutaneous burns, respiratory injury was frequent. The initial clinical signs may be helpful to predict pulmonary complications.

Ethylene glycol poisoning treated by intravenous 4-methylpyrazole.

A 19-year-old woman was admitted 45 min after ethylene glycol (EG) ingestion. The initial serum EG concentration was 1.34 g/l (21.6 mmol/l), the anion gap 14.5, and the osmolal gap 24. Renal function was preserved (serum creatinine 75.1 micromol/l). As the patient was seen soon after poisoning, before the development of metabolic acidosis, therapy with 4-methylpyrazole (4-MP) was proposed as an antidote. 4-MP was administered via the intravenous route (7 mg/kg as loading dose, followed by 3.6, 1.2, 0.6, and 0.6 mg/kg at intervals of 12 h). 4-MP alone was effective in preventing EG biotransformation to toxic metabolites (absence of metabolic acidosis and renal injury). Ethanol therapy, hemodialysis, and sodium bicarbonate administration were not required. The half-life of EG during 4-MP therapy was 11 h, with a mean EG renal clearance of 26.9 ml/min, and a total of 65.3 g EG was eliminated unchanged in the urine. 4-MP therapy was also well tolerated.

Hyperthermia complicating tricyclic antidepressant overdose.

We observed a 51-year-old woman who was admitted for severe amitriptyline overdose. Besides major cardiovascular complications, the patient developed severe hyperpyrexia with a central body temperature of more than 43 degrees C for 5 h. The patient died on day 3 from cardiocirculatory collapse and arrhythmias. Hyperthermia was unresponsive to cooling with ice water, gastric lavage, muscle relaxation, and dantrolene and bromocriptine administration. The possible mechanisms of refractory hyperthermia are discussed.