Variation in timing of decisions to withdraw life-sustaining treatment in adult ICU patients from three centres in different geographies: Do clinical factors explain the difference?

Background: Decisions to withdraw life-sustaining treatment (WLST) are common in intensive care units (ICUs). Clinical and non-clinical factors are important, although the extent to which each plays a part is uncertain. Objectives: To determine whether the timing of decisions to WLST varies between ICUs in a single centre in three countries and whether differences in timing are explained by differences in clinical decision-making. Methods: The study involved a convenience sample of three adult ICUs - one in each of the UK, USA and South Africa (SA). Data were prospectively collected on patients whose life-sustaining treatment was withdrawn over three months. The timing of decisions was collected, as were patients' premorbid functional status and illness severity 24 hours prior to decision to WLST. Multivariate analysis was used to identify factors associated with decisions to WLST. Clinicians participated in interviews involving hypothetical case studies devoid of non-clinical factors. Results: Deaths following WLST accounted for 23% of all deaths during the study period at the USA site v. 37% (UK site) and 70% (SA site) (p<0.0010 across the three sites). Length of stay (LOS) prior to WLST decision varied between sites. Controlling for performance status, age, and illness severity, study site predicted LOS prior to decision (p<0.0010). In the hypothetical cases, LOS prior to WLST was higher for USA clinicians (p<0.017). Conclusion: There is variation in the proportion of ICU patients in whom WLST occurs and the timing of these decisions between sites; differences in clinical decision-making may explain the variation observed, although clinical and non-clinical factors are inextricably linked. Contributions of the study: This study has identified variation in the timing of decisions to withdraw life-sustaining treatment in adult ICUs in three centres in three different healthcare systems. Although differences in clinical decision-making likely explain some of the variation, non-clinical factors (relating to the society in which the clinicians live and work) may also play a part.

Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use.

OBJECTIVE: To determine whether 1) combined oral contraceptive (COC) use affects serum levels of valproate (VPA) as well as lamotrigine (LTG) and 2) the naturally occurring high (mid-luteal) and low (early-mid follicular) reproductive steroid level phases of the menstrual cycle might affect antiepileptic drug levels as well. METHODS: This investigation compared serum antiepileptic drug levels at two timepoints during a single menstrual cycle in four groups of women with epilepsy: 12 on VPA, 12 on VPA plus COC (VPA-COC), 12 on LTG, and 12 on LTG plus COC (LTG-COC). RESULTS: Both VPA and LTG levels were lower (p < 0.01) on active COC than on inactive pill with median declines of 23.4% for the VPA-COC group and 32.6% for the LTG-COC group. Serum LTG levels showed a notable but not significant 31.3% median decline during the mid-luteal phase compared to the early-mid follicular phase in the non-COC group. The non-COC valproate group showed the least change of any group between the two measured timepoints with a decline of 8.3% (p = NS). CONCLUSIONS: The findings suggest that valproate (VPA), like lamotrigine (LTG), has substantially and significantly lower serum levels while women take active combined oral contraceptives as compared to inactive pills. Larger sample sizes will be required to determine whether LTG levels may drop significantly also during the luteal (high steroid) phase of natural menstrual cycles and whether VPA levels may show greater stability in levels across the phases of the menstrual cycle.

Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy.

PURPOSE: The occurrence of hypoxemia in adults with partial seizures has not been systematically explored. Our aim was to study in detail the temporal dynamics of this specific type of ictal-associated hypoxemia. METHODS: During long-term video/EEG monitoring (LTM), patients underwent monitoring of oxygen saturation using a digital Spo2 (pulse oximeter) transducer. Six patients (nine seizures) were identified with oxygen desaturations after the onset of partial seizure activity. RESULTS: Complex partial seizures originated from both left and right temporal lobes. Mean seizure duration (+/-SD) was 73 +/- 18 s. Mean Spo2 desaturation duration was 76 +/- 19 s. The onset of oxygen desaturation followed seizure onset with a mean delay of 43 +/- 16 s. Mean (+/-SD) Spo2 nadir was 83 +/- 5% (range, 77-91%), occurring an average of 35 +/- 12 s after the onset of the desaturation. One seizure was associated with prolonged and recurrent Spo2 desaturations. CONCLUSIONS: Partial seizures may be associated with prominent oxygen desaturations. The comparable duration of each seizure and its subsequent desaturation suggests a close mechanistic (possibly causal) relation. Spo2 monitoring provides an added means for seizure detection that may increase LTM yield. These observations also raise the possibility that ictal ventilatory dysfunction could play a role in certain cases of sudden unexpected death in epilepsy in adults with partial seizures.

Postictal heart rate oscillations in partial epilepsy.

We report postictal heart rate oscillations in a heterogeneous group of patients with partial epilepsy. This pattern is marked by the appearance of transient but prominent low-frequency heart rate oscillations (0.01 to 0.1 Hz) immediately after 5 of 11 seizures recorded in 5 patients. This finding may be a marker of neuroautonomic instability and, therefore, may have implications for understanding perturbations of heart rate control associated with partial seizures.

Depth of EEG suppression and outcome in barbiturate anesthetic treatment for refractory status epilepticus.

PURPOSE: Barbiturate anesthetic treatment of patients with refractory status epilepticus (RSE) is often titrated to a burst-suppression record on the EEG. We sought to determine whether the depth of EEG suppression correlated with persistent seizure control in such patients. METHODS: We reviewed the EEGs and clinical course of patients treated with pentobarbital (PTB) for RSE. Persistent seizure control or relapse to status epilepticus after the taper of PTB was determined with reference to the depth of EEG suppression during treatment. RESULTS: Of 35 patients tapering PTB, persistent seizure control was achieved in six of 12 patients reaching a burst-suppression record at greatest depth of EEG suppression and in 17 of 20 patients reaching a "flat" record; three patients with neither pattern had persistent control. Survival also was somewhat better in the more suppressed group. Isolated epileptiform discharges during the barbiturate infusion did not correlate with outcome. Recurrence of electrographic status after PTB taper predicted clinical relapse. CONCLUSIONS: The EEG is important in managing PTB treatment for patients with RSE. Some period of intense seizure and EEG suppression may help in preventing relapse of status after the PTB taper. It is not necessary to suppress all epileptiform discharges, but persistent clinical and EEG monitoring is necessary to avoid relapses.

Technical implementation and clinical findings/results of monitoring oxygen saturation in patients referred for long-term EEG monitoring.

Recent technical developments allow the recording of a patient's oxygen saturation (SpO2) simultaneously with intensive long-term EEG monitoring (LTM). Clinically significant information from this enhanced multi-system physiological monitoring device can contribute to more accurate diagnoses in patients referred for LTM. This report covers the technical usage of combined SpO2/EEG recordings in a small group of patients. Clinically, the findings on the SpO2 monitor helped to define the diagnosis in many of these patients. In a few, the SpO2 changes were diagnostic in their own right and prompted referral to our Sleep Disorders Laboratory. From a research aspect, the details of the morphology and timing of the oxygen desaturations and EEG show several interesting relationships with respect to the dynamics of seizure semiology and respiratory physiology.

Relapse and survival after barbiturate anesthetic treatment of refractory status epilepticus.

PURPOSE: Pentobarbital is standard treatment for refractory status epilepticus (SE) and is almost uniformly effective, but the morbidity of treatment and the mortality of refractory SE are high. Recurrence of SE after pentobarbital discontinuation may predict a worsened outcome. We sought to determine the optimal use of barbiturate anesthetic treatment of refractory SE. METHODS: We reviewed 44 episodes of barbiturate anesthetic treatment for refractory SE in 40 patients, seeking factors predicting freedom from relapse to clinical or electrographic SE after treatment and predicting survival. RESULTS: Eight of 9 patients with relapse of seizures after barbiturate treatment died, whereas only 9 of 26 with persistently controlled seizures died (p < 0.005). Both likelihood of relapse and survival correlated strongly with etiology, with 19 of 20 patients with chronic epilepsy, infections, or focal lesions having good control as compared with 2 of 9 with multiple medical problems (p < 0.001). Treatment delay did not predict a worsened outcome. Hypotension caused dose reduction but never required treatment discontinuation. Patients with more prolonged treatment and those receiving phenobarbital (PB) at the time of pentobarbital taper were less likely to relapse. CONCLUSIONS: Relapse of SE after barbiturate anesthetic treatment is a poor prognostic sign and should be prevented, if possible. Etiology was the primary predictor of outcome, but more prolonged treatment and the use of PB during pentobarbital withdrawal appeared to provide protection against relapse.

Acute Lyme neuropathy presenting with polyradicular pain, abdominal protrusion, and cranial neuropathy.

A 53-year-old man developed multifocal radicular pain. The diagnosis of Lyme neuroborreliosis was delayed until bifacial paresis and right lower abdominal wall weakness developed, prompting further evaluation. Cerebrospinal fluid (CSF) examination showed aseptic meningitis. Antibodies directed against Borrelia burgdorferi were present in the serum; higher titers were present in the CSF, indicating local antibody production. Electrophysiologic studies showed both an axonal polyradiculopathy as well as demyelinative facial palsy. Ceftriaxone therapy led to marked improvement in pain and facial palsies.