[An acidosis not so basic]. / Une acidose pas si basique.

We present the case of a four-year-old girl, who was hospitalized in intensive care unit for a coma resulting from metabolic acidosis with increased anion gap. The patient was treated for short bowel syndrome, following necrotising enterocolitis, which occurred 51 days after birth. In our initial evaluation of the patient's metabolic acidosis, we were unable to identify the cause of the increased anion gap. Urinary organic acids chromatography identified a large peak of lactate (quantified at 15 mmol/mol of creatiniuria), as well as its metabolites. The discrepancy between normal blood lactate concentration assayed by enzymatic assay, and the large amount of lactate found by gas-chromatography/mass spectrometry (GC/MS) in urine highlights the limit of the stereospecificity of enzymatic assays. Indeed, most lactates assay use enzymatic assays that are specific for L-lactate, whereas organic acids chromatography, whose column is mostly achiral, can detect both stereoisomers, D- and L-lactate. Organic acids in urine analysis, in addition to the clinical context, suggested a diagnosis of D-lactic acidosis. Following a review of the physiopathology and treatment of short bowel syndrome, we will discuss the mechanism and diagnosis of the D-lactic acidosis in our patient. This case highlights the need to perform an organic acid profile in urine in the presence of any unexplained increased anion gap to determine its cause.

Is circadian rhythmicity a prerequisite to coma recovery? Circadian recovery concomitant to cognitive improvement in two comatose patients.

Circadian rhythmicity (CR) is involved in the regulation of all integrated functions, from sleep-wake cycle regulation to metabolic function, mood and cognition. However, the interdependence of CR, cognition and consciousness has been poorly addressed. To clarify the state of CR in coma and to determine the chronological relationship between its recovery and consciousness after brain lesions, we conducted a longitudinal observational study investigating how the state of CR was chronologically related with the recovery of behavioural wakefulness, cognition and/or awareness. Among 16 acute comatose patients, we recruited two 37-year-old patients with a persistent disorder of consciousness, presenting diencephalic lesions caused by severe traumatic brain injuries. Two biological urinary markers of CR were explored every 2 hours during 24 hours (6-sulfatoxymelatonin, free cortisol) with a dedicated methodology to extract the endogenous component of rhythmicity (environmental light recording, near-constant-routine protocol, control of beta-blockers). They presented an initial absence of rhythmic secretions and a recovered CR 7-8 months later. This recovery was not associated with the restoration of behavioural wakefulness, but with an improvement of cognition and awareness (up to the minimally conscious state). MRI showed a lesion pattern compatible with the interruption of either the main hypothalamic-sympathetic pathway or the accessory habenular pathway. These results suggest that CR may be a prerequisite for coma recovery with a potential but still unproven favourable effect on brain function of the resorted circadian melatonin secretion and/or the functional recovery of the suprachiasmatic nucleus (SCN). Assessing circadian functions by urinary melatonin should be further explored as a biomarker of cognition reappearance and investigated to prognosticate functional recovery.

Decriminalization of cannabis--potential risks for children?

The legalization of cannabis for medicinal purposes is becoming increasingly widespread worldwide. The anticipated growing ease of access to cannabis may create an increased risk for passive and/or active ingestion by children. We report a case of a 1.5-year-old infant who presented with unexplained coma that was later proved to be associated with the ingestion of cannabis. This case highlights the importance of considering cannabis ingestion in the differential diagnosis of infantile and toddler coma and the need for public education regarding the risks of childhood exposure in the light of the legalization of cannabis for medical purposes and its greater availability.

Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure.

Reports of toxicity secondary to Kratom are rare and lack of diagnostic testing in human specimens has prevented confirmatory explanation of observed clinical effects. We present a novel case of serious human toxicity following Kratom use confirmed via quantitative analysis of urine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. A 64 year-old male was witnessed to have a seizure at home following kratom consumption. Upon arrival to the emergency department (ED), the patient was unresponsive. While in the ED, the patient sustained a second seizure. He was intubated to protect his airway. The remainder of his hospital course was uneventful. A urine specimen was collected shortly after admission and sent for analysis. The mitragynine concentration in the urine was 167 ± 15 ng/ml. We report a rare case of Kratom toxicity characterized by a seizure and coma confirmed by urinary analysis of mitragynine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. The proposed mechanism for this reaction is unclear but suggested mechanisms include adenosine binding or stimulation of adrenergic and/or serotonergic receptors similar to tramadol.

Kearns-Sayre syndrome presenting as 2-oxoadipic aciduria.

A patient with 2-oxoadipic aciduria and 2-aminoadipic aciduria presented at 2 years of age with manifestations typical of organic acidemia, episodes of ketosis and acidosis, progressive to coma. This resolved and the key metabolites disappeared from the urine and blood. At 9 years of age she developed typical Kearns-Sayre syndrome with complete heart block, retinopathy, and ophthalmoplegia. Southern blot revealed a deletion in the mitochondrial genome.

Alkaline diuresis for acute poisoning with chlorophenoxy herbicides and ioxynil.

The relation between blood chlorophenoxy herbicide and ioxynil concentrations and toxicity, and the effect of alkaline diuresis on outcome, have been studied in 41 patients. More than one herbicide was found in 38 cases. 6 of 30 patients who had ingested chlorophenoxy compounds alone died; 16 patients (mostly in grade 3-4 coma) had alkaline diuresis and 15 survived. 7 of 11 patients who had co-ingested ioxynil died; 3 had alkaline diuresis and all survived. Alkaline diuresis reduced plasma chlorophenoxy half-lives to values observed after doses that had no adverse effects (ie, below 30 h), but did not influence ioxynil clearance. Alkaline diuresis should be used to treat acute poisoning with chlorophenoxy herbicides or ioxynil in the presence of coma or other poor prognostic indicators, such as acidaemia, or if plasma total chlorophenoxy concentrations are 0.5 g/l or more.

Ingestion of cannabis: a cause of coma in children.

Previous reports of accidental ingestion of cannabis by children are rare. None has reported coma, although one described a stuporous state that required assisted ventilation. Over the past four years, the staff of British Columbia's Children's Hospital has managed six children with cannabis toxicity, three of whom presented in coma, including one with airway obstruction. Recurring diagnostic features included rapid onset of drowsiness, moderate pupil dilation, hypotonia, lid lag, and the presence of small granules or leaves in the mouth. Confirmation was obtained by positive urine screening for cannabinoids. The six cases described emphasize the need for emergency physician awareness of possible diagnostic criteria, the potential severity of intoxication, and the need for prevention through parent education.

Lactosuria - a new metabolic feature of severe cerebrocranial trauma.

Under controlled dietary conditions the urinary excretion of lactose was studied in 15 healthy persons, 15 patients with cerebrocranial trauma and 15 patients with extracranial trauma. Urinary lactose levels were found to be markedly increased in patients with head injury and ranged from 10.3 to 147.7 mg/24 h with a mean 63.4 mg/24 h in contrast to patients with other injuries (3.1 to 17.0 mg/24 h, mean 9.4 mg/24 h; P less than 0.001), and healthy individuals (3.3 to 17.93 mg/24 h, mean 7.6 mg/24h; P less than 0.001). In the head injury group the lowest values were found in drowsy or disoriented patients with cerebral concussion and the highest in comatose subjects. The level of lactosuria decreases after approximately 12 to 16 days to normal levels even when the patient remains unconscious. An earlier return to normal excretion parallels or preceeds the reappearance of consciousness. Unlike alimentary lactosuria, caused by ingestion of milk or other dairy products in large quantities, the elevated lactose levels in head injury patients were not usually accompanied by a comparable rise in galactose excretion, mean 11.45 mg/24 h versus 9.17 mg/24 h in controls; P less than 0.2. The mechanism of enhanced lactose excretion in severe cerebrocranial trauma remains unknown. It is suggested that it may be associated with either an increased catabolism of brain gangliosides or a stimulated lactose synthesis in peripheral tissues probably due to the participation of the lactogenic hormone prolactin.