Colchicine overdose with coingestion of nonsteroidal antiinflammatory drugs.

Colchicine has a low therapeutic index. Its toxic effects generally occur at doses ≥ 0.5 mg/kg. We present the case of a 39-year-old female with toxicity following ingestion of 0.28 mg/kg. The patient presented to the emergency department (ED) with severe nausea, vomiting, and abdominal pain following an intentional multidrug ingestion that included colchicine, indomethacin, and zopiclone. Despite toxicologic management and supportive care, admission to the intensive care unit was required for clinical deterioration and symptom management. Shock and multiorgan failure resulted, with death occurring 52 hours postingestion. Although the toxic effects of colchicine are well documented, mortality caused by low doses is relatively uncommon. Management of toxicity consists of early diagnosis, decontamination, and supportive measures. Toxicity may be enhanced by drug interactions inhibiting metabolic enzymes or poor excretion due to renal failure. In this case, the ingestion of a nonsteroidal antiinflammatory drug and the associated volume depletion from the gastrointestinal effects of colchicine may have contributed to renal dysfunction, exacerbating the toxicity of colchicine. This ingestion of a relatively small dose of colchicine led to severe toxicity. Treatment options for colchicine toxicity are limited.

Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine.

INTRODUCTION: Cardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs. METHODS: This was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 µg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs. RESULTS: We enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P=0.033). CONCLUSIONS: Troponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality. TRIAL REGISTRATION: Controlled-trials.com ISRCTN94845869.

High-grade intracranial chondrosarcoma presenting with haemorrhage.

Chondrosarcomas are rare sarcomas that produce malignant cartilage, infrequently arising as a primary intracranial tumour. We present a patient with intracranial chondrosarcoma with intratumoural haemorrhage arising in an unusual location and with unusual imaging findings. A 46-year-old man presented with headache, nausea, and vomiting over the previous 24 hours. Physical and neurological examinations were normal. Cranial CT scans and MRI revealed a large right pre-frontal (subdural) and interhemispheric heterogeneous density associated with a frontal, partially calcified mass and midline shift. An awake craniotomy was performed. With the intra-operative quick section favouring subdural hematoma, the lesion was subtotally resected. Follow-up imaging confirmed residual mass. Pathology examination revealed a high-grade malignant neoplasm with chondroid differentiation, diagnosed as conventional Grade III chondrosarcoma. The patient was referred to oncology for follow-up and radiation therapy. Intracranial chondrosarcoma was first reported in 1899, and since then continues to be an extremely rare malignancy of the brain. These tumours commonly present as extra-axial masses, originating from the skull base, and produce symptoms due to progressive enlargement and compression of local structures. Unusual presentations of these tumours, such as vascularity, intratumoural haemorrhage, and intra-axial location, may complicate pre-surgical decision making by altering the provisional diagnosis prior to intervention. This patient emphasises the importance of careful analysis and incorporation of imaging findings into surgical decision making. Specific imaging characteristics that, in such unusual situations, are suggestive of chondrosarcoma should motivate an aggressive surgical approach to optimise adjuvant interventions.

Detection of critical illness-related corticosteroid insufficiency using 1 µg adrenocorticotropic hormone test.

Our objectives were to determine the incidence of critical illness-related corticosteroid insufficiency (CIRCI) in patients with septic shock using a 1 µg corticotropin (ACTH) test and to describe their clinical outcomes. We retrospectively identified 219 consecutive patients with septic shock assessed for CIRCI with a 1 µg ACTH test. Standardized testing involved plasma cortisol measurements at baseline (T0) and at 30 min (T30) and 60 min (T60) after ACTH administration. The maximal increase in cortisol (Δ max) was calculated as the difference between T0 and the highest cortisol value at T30 or T60. Critical illness-related corticosteroid insufficiency was defined as Δ max less than 9 µg/dL after ACTH administration. The mean age of the cohort was 63.0 ± 15.8 years, mean Acute Physiology and Chronic Health Evaluation II score was 26.3 ± 8.1, 85.6% were mechanically ventilated, and the mean number of organ failures was 3.0 ± 1.2. Critical illness-related corticosteroid insufficiency was diagnosed in 70.8% of patients. Twenty-eight-day mortality was highest in patients with baseline cortisol greater than 65 µg/dL (62.5%) and in those with baseline cortisol 34 µg/dL or greater and Δ max less than 9 µg/dL (50.0%). There was no difference in mortality in patients with and without CIRCI (53.9% vs. 36.4%, P = 0.08). Corticosteroids were administered to 69.4% of patients for 5.3 ± 3.6 days. For patients with CIRCI, intensive care unit mortality was similar for those who received corticosteroids compared with those who did not (46.0% vs. 25.0%, P = 0.166). The incidence of CIRCI based on 1 µg ACTH was high in this septic shock cohort. The highest mortality rates were observed in patients with high baseline cortisol and in those who failed to respond appropriately to ACTH. The administration of corticosteroids was not associated with a reduction in mortality.

Agreement in electrocardiogram interpretation in patients with septic shock.

OBJECTIVE: The reliability of electrocardiogram interpretation to diagnose myocardial ischemia in critically ill patients is unclear. In adults with septic shock, we assessed intra- and inter-rater agreement of electrocardiogram interpretation, and the effect of knowledge of troponin values on these interpretations. DESIGN: Prospective substudy of a randomized trial of vasopressin vs. norepinephrine in septic shock. SETTING: Nine Canadian intensive care units. PATIENTS: Adults with septic shock requiring at least 5 µg/min of norepinephrine for 6 hrs. INTERVENTIONS: Twelve-lead electrocardiograms were recorded before study drug, and 6 hrs, 2 days, and 4 days after study drug initiation. MEASUREMENTS: Two physician readers, blinded to patient data and group, independently interpreted electrocardiograms on three occasions (first two readings were blinded to patient data; third reading was unblinded to troponin). To calibrate and refine definitions, both readers initially reviewed 25 trial electrocardiograms representing normal to abnormal. Cohen's Kappa and the φ statistic were used to analyze intra- and inter-rater agreement. RESULTS: One hundred twenty-one patients (62.2 ± 16.5 yrs, Acute Physiology and Chronic Health Evaluation II 28.6 ± 7.7) had 373 electrocardiograms. Blinded to troponin, readers 1 and 2 interpreted 46.4% and 30.0% of electrocardiograms as normal, and 15.3% and 12.3% as ischemic, respectively. Intrarater agreement was moderate for overall ischemia (κ 0.54 and 0.58), moderate/good for "normal" (κ 0.69 and 0.55), fair to good for specific signs of ischemia (ST elevation, T inversion, and Q waves, reader 1 κ 0.40 to 0.69; reader 2 κ 0.56 to 0.70); and good/very good for atrial arrhythmias (κ 0.84 and 0.79) and bundle branch block (κ 0.88 and 0.79). Inter-rater agreement was fair for ischemia (κ 0.29), moderate for ST elevation (κ 0.48), T inversion (κ 0.52), and Q waves (κ 0.44), good for bundle branch block (κ 0.78), and very good for atrial arrhythmias (κ 0.83). Inter-rater agreement for ischemia improved from fair to moderate (κ 0.52, p = .028) when unblinded to troponin. CONCLUSIONS: In patients with septic shock, inter-rater agreement of electrocardiogram interpretation for myocardial ischemia was fair, and improved with troponin knowledge.