Polonium-210 poisoning: a first-hand account.

BACKGROUND: Polonium-210 ((210)Po) gained widespread notoriety after the poisoning and subsequent death of Mr Alexander Litvinenko in London, UK, in 2006. Exposure to (210)Po resulted initially in a clinical course that was indistinguishable from infection or exposure to chemical toxins, such as thallium. METHODS: A 43-year-old man presented to his local hospital with acute abdominal pain, diarrhoea, and vomiting, and was admitted to the hospital because of dehydration and persistent gastrointestinal symptoms. He was initially diagnosed with gastroenteritis and treated with antibiotics. Clostridium difficile toxin was subsequently detected in his stools, which is when he first raised the possibility of being poisoned and revealed his background and former identity, having been admitted under a new identity with which he had been provided on being granted asylum in the UK. Within 6 days, the patient had developed thrombocytopenia and neutropenia, which was initially thought to be drug induced. By 2 weeks, in addition to bone marrow failure, he had evidence of alopecia and mucositis. Thallium poisoning was suspected and investigated but ultimately dismissed because blood levels of thallium, although raised, were lower than toxic concentrations. The patient continued to deteriorate and within 3 weeks had developed multiple organ failure requiring ventilation, haemofiltration, and cardiac support, associated with a drop in consciousness. On the 23rd day after he first became ill, he suffered a pulseless electrical activity cardiorespiratory arrest from which he could not be resuscitated and was pronounced dead. FINDINGS: Urine analysis using gamma-ray spectroscopy on day 22 showed a characteristic 803 keV photon emission, raising the possibility of (210)Po poisoning. Results of confirmatory analysis that became available after the patient's death established the presence of (210)Po at concentrations about 10(9)-times higher than normal background levels. Post-mortem tissue analyses showed autolysis and retention of (210)Po at lethal doses in several organs. On the basis of the measured amounts and tissue distribution of (210)Po, it was estimated that the patient had ingested several 1000 million becquerels (a few GBq), probably as a soluble salt (eg, chloride), which delivered very high and fatal radiation doses over a period of a few days. INTERPRETATION: Early symptoms of (210)Po poisoning are indistinguishable from those of a wide range of chemical toxins. Hence, the diagnosis can be delayed and even missed without a high degree of suspicion. Although body surface scanning with a standard Geiger counter was unable to detect the radiation emitted by (210)Po, an atypical clinical course prompted active consideration of poisoning with radioactive material, with the diagnosis ultimately being made with gamma-ray spectroscopy of a urine sample. FUNDING: UK NHS, Public Health England, and the UK Department of Health.

Medication errors: a prospective cohort study of hand-written and computerised physician order entry in the intensive care unit.

INTRODUCTION: The study aimed to compare the impact of computerised physician order entry (CPOE) without decision support with hand-written prescribing (HWP) on the frequency, type and outcome of medication errors (MEs) in the intensive care unit. METHODS: Details of MEs were collected before, and at several time points after, the change from HWP to CPOE. The study was conducted in a London teaching hospital's 22-bedded general ICU. The sampling periods were 28 weeks before and 2, 10, 25 and 37 weeks after introduction of CPOE. The unit pharmacist prospectively recorded details of MEs and the total number of drugs prescribed daily during the data collection periods, during the course of his normal chart review. RESULTS: The total proportion of MEs was significantly lower with CPOE (117 errors from 2429 prescriptions, 4.8%) than with HWP (69 errors from 1036 prescriptions, 6.7%) (p < 0.04). The proportion of errors reduced with time following the introduction of CPOE (p < 0.001). Two errors with CPOE led to patient harm requiring an increase in length of stay and, if administered, three prescriptions with CPOE could potentially have led to permanent harm or death. Differences in the types of error between systems were noted. There was a reduction in major/moderate patient outcomes with CPOE when non-intercepted and intercepted errors were combined (p = 0.01). The mean baseline APACHE II score did not differ significantly between the HWP and the CPOE periods (19.4 versus 20.0, respectively, p = 0.71). CONCLUSION: Introduction of CPOE was associated with a reduction in the proportion of MEs and an improvement in the overall patient outcome score (if intercepted errors were included). Moderate and major errors, however, remain a significant concern with CPOE.

Noninvasive measurement of cerebral blood flow in adults using near-infrared spectroscopy and indocyanine green: a pilot study.

This pilot study was designed to determine the feasibility of measuring cerebral blood flow noninvasively after an intravenous bolus of indocyanine green using near-infrared spectroscopy and pulse dye-densitometry. Feasibility aside, this study did not attempt to validate the measured values of cerebral blood flow against an established method of measurement. Twelve healthy volunteers were investigated after peripheral intravenous injection of indocyanine green. Arterial and cerebral changes in indocyanine green concentration were measured using pulse dye-densitometry and near-infrared spectroscopy, respectively. Two methods of calculating cerebral blood flow were used, and a blood flow index was also estimated. Absolute cerebral blood flow was calculated using a modification of the Fick principle and a deconvolution algorithm to derive the impulse residue function. Mean (range) estimated cerebral blood flow for the Fick method was 8.2 mL/100 g/min (4.2-16.2 mL/100 g/min) and 8.3 mL/100 g/min (4.7-15.3 mL/100 g/min) for the impulse residue function method. The impulse residue function method provided a more precise intrasubject estimation of cerebral blood flow compared with the modified Fick principle, with a coefficient of variation of 10.1% versus 25.5%. The blood flow index was 8.6 mg/sec (range: 5.6-17.3 mg/sec) with an intrasubject coefficient of variation of 12.0%. Estimation of cerebral blood flow using near-infrared spectroscopy and pulse dye-densitometry can be made at the bedside after intravenous injection of indocyanine green, and the precision can be improved using a deconvolution algorithm. Notwithstanding the low values obtained for absolute cerebral blood flow, further investigation and validation of this bedside technique is warranted.

Central venous and bladder pressure reflect transdiaphragmatic pressure during pressure support ventilation.

STUDY OBJECTIVES: To determine whether the change in bladder pressure (Pblad) and central venous pressure (Pcvp) may reflect the changes in esophageal pressure (Pes) and gastric pressure (Pgas) when inspiratory pressure support (IPS) is altered. DESIGN: Prospective clinical study. SETTING: The ICUs of a teaching hospital. PATIENTS: Ten patients currently receiving IPS ventilation via a tracheostomy or an endotracheal tube who already had bladder and central venous catheters in situ. MEASUREMENTS AND RESULTS: Airway pressure, Pes, Pgas, Pcvp, Pblad, and flow were measured at the original IPS setting. IPS then was reduced by 5-cm H(2)O increments until IPS was zero or was at the minimum pressure that could be tolerated by each patient. At each level of IPS, pressures and flow were measured at steady-state breathing. The maximum pressure difference for each pressure during inspiration was calculated. We found that the Delta Pblad correlated closely with the Delta Pgas (r = 0.904) and that the Delta Pes correlated with the Delta Pcvp (r = 0.951). When the Delta Pcvp - Delta Pblad was compared with the transdiaphragmatic pressure for each patient as the IPS was altered, the correlation coefficients varied from 0.952 to 0.999. CONCLUSION: Although absolute values for the Delta Pcvp during mechanical ventilation do not always reflect the Delta Pes, useful information can be obtained from this route. In individual patients, the two sites of measurement followed each other when IPS was changed, enabling a bedside assessment of the response to reducing respiratory support.