Reliability of standard pupillometry practice in neurocritical care: an observational, double-blinded study.

BACKGROUND: In critical care units, pupil examination is an important clinical parameter for patient monitoring. Current practice is to use a penlight to observe the pupillary light reflex. The result seems to be a subjective measurement, with low precision and reproducibility. Several quantitative pupillometer devices are now available, although their use is primarily restricted to the research setting. To assess whether adoption of these technologies would benefit the clinic, we compared automated quantitative pupillometry with the standard clinical pupillary examination currently used for brain-injured patients. METHODS: In order to determine inter-observer agreement of the device, we performed repetitive measurements in 200 healthy volunteers ranging in age from 21 to 58 years, providing a total of 400 paired (alternative right eye, left eye) measurements under a wide variety of ambient light condition with NeuroLight Algiscan pupillometer. During another period, we conducted a prospective, observational, double-blinded study in two neurocritical care units. Patients admitted to these units after an acute brain injury were included. Initially, nursing staff measured pupil size, anisocoria and pupillary light reflex. A blinded physician subsequently performed measurement using an automated pupillometer. RESULTS: In 200 healthy volunteers, intra-class correlation coefficient for maximum resting pupil size was 0.95 (IC: 0.93-0.97) and for minimum pupil size after light stimulation 0.87 (0.83-0.89). We found only 3-pupil asymmetry (≥ 1 mm) in these volunteers (1.5% of the population) with a clear pupil asymmetry during clinical inspection. The mean pupil light reactivity was 40 ± 7%. In 59 patients, 406 pupillary measurements were prospectively performed. Concordance between measurements for pupil size collected using the pupillometer, versus subjective assessment, was poor (Spearmen's rho = 0.75, IC: 0.70-0.79; P < 0.001). Nursing staff failed to diagnose half of the cases (15/30) of anisocoria detected using the pupillometer device. A global rate of discordance of 18% (72/406) was found between the two techniques when assessing the pupillary light reflex. For measurements with small pupils (diameters <2 mm) the error rate was 39% (24/61). CONCLUSION: Standard practice in pupillary monitoring yields inaccurate data. Automated quantitative pupillometry is a more reliable method with which to collect pupillary measurements at the bedside.

Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity.

INTRODUCTION: Recent data on newborn animals exposed to anesthetics have raised safety concerns regarding anesthesia practices in young children. Indeed, studies on rodents have demonstrated a widespread increase in brain apoptosis shortly after exposure to sevoflurane, followed by long-term neurologic impairment. In this context, we aimed to evaluate the protective effect of rh-EPO, a potent neuroprotective agent, in rat pups exposed to sevoflurane. MATERIAL AND METHODS: At postnatal day 7, 75 rat pups were allocated into three groups: SEVO + EPO (n = 27) exposed to sevoflurane 2 vol% (0.5 MAC) for 6 h in an air/O2 mixture (60/40) + 5000 UI.kg(-1) rh-EPO IP; SEVO (n = 27) exposed to sevoflurane + vehicle IP; and CONTROL (n = 21) exposed to the mixture without sevoflurane + vehicle IP. Three days after anesthesia (D10), apoptosis was quantified on brain extract with TUNEL method and caspase 3. NGF and BDNF expression was determined by Western blotting. Rats reaching adulthood were evaluated in terms of exploration capacities (object exploration duration) together with spatial and object learning (water maze and novel object test). RESULTS: Sevoflurane exposure impaired normal behavior in adult rats by reducing the exploratory capacities during the novel object test and impaired both spatial and object learning capacities in adult rats (water maze, ratio time to find platform 3rd trial/1st trial: 1.1 ± 0.2 vs 0.4 ± 0.1; n = 9, SEVO vs CONTROL; P = 0.01). Rh-EPO reduced sevoflurane-induced behavior and learning abnormalities in adult rats (water maze, ratio time to find platform 3rd trial/1st trial: 0.3 ± 0.1 vs 1.1 ± 0.2; n = 9, SEVO + EPO vs SEVO; P = 0.01). Three days after anesthesia, rh-EPO prevented sevoflurane-induced brain apoptosis (5 ± 3 vs 35 ± 6 apoptotic cells·mm(-2) ; n = 6, SEVO + EPO vs SEVO; P = 0.01) and elevation of caspase three level and significantly increased the brain expression of BDNF and NGF (n = 6, SEVO + EPO vs SEVO; P = 0.01). CONCLUSION: Six hours of sevoflurane anesthesia in newborn rats induces significant long-term cognitive impairment. A single administration of rh-EPO immediately after postnatal exposure to sevoflurane reduces both early activation of apoptotic phenomenon and late onset of neurologic disorders.

Erythropoietin Pretreatment of Transplanted Endothelial Colony-Forming Cells Enhances Recovery in a Cerebral Ischemia Model by Increasing Their Homing Ability: A SPECT/CT Study.

Endothelial colony-forming cells (ECFCs) are promising candidates for cell therapy of ischemic diseases, as less than 10% of patients with an ischemic stroke are eligible for thrombolysis. We previously reported that erythropoietin priming of ECFCs increased their in vitro and in vivo angiogenic properties in mice with hindlimb ischemia. The present study used SPECT/CT to evaluate whether priming of ECFCs with erythropoietin could enhance their homing to the ischemic site after transient middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and potentiate their protective or regenerative effect on blood-brain barrier (BBB) disruption, cerebral apoptosis, and cerebral blood flow (CBF). METHODS: Rats underwent a 1-h MCAO followed by reperfusion and then 1 d after MCAO received an intravenous injection of either PBS (control, n = 10), PBS-primed ECFCs (ECFCPBS, n = 13), or erythropoietin-primed ECFCs (ECFCEPO, n = 10). ECFC homing and the effect on BBB disruption, cerebral apoptosis, and CBF were evaluated by SPECT/CT up to 14 d after MCAO. The results were expressed as median ± interquartile range for ipsilateral-to-contralateral ratio of the activity in middle cerebral artery-vascularized territories in each hemisphere. Histologic evaluation of neuronal survival and astrocytic proliferation was performed on day 14. RESULTS: Erythropoietin priming increased homing of ECFCs to the ischemic hemisphere (ECFCPBS, 111.0% ± 16.0%; ECFCEPO, 146.5% ± 13.3%). BBB disruption was significantly reduced (control, 387% ± 153%; ECFCPBS, 151% ± 46% [P < 0.05]; ECFCEPO, 112% ± 9% [P < 0.001]) and correlated negatively with ECFC homing (Pearson r = -0.6930, P = 0.0002). Cerebral apoptosis was significantly reduced (control, 161% ± 10%; ECFCPBS, 141% ± 9% [P < 0.05]; ECFCEPO,118% ± 5% [P < 0.001]) and correlated negatively with ECFC homing (r = -0.7251, P < 0.0001). CBF was significantly restored with ECFCs and almost totally so with erythropoietin priming (control, 72% ± 2%; ECFCPBS, 90% ± 4% [P < 0.01]; ECFCEPO, 99% ± 4% [P < 0.001]) and correlated positively with ECFC homing (r = 0.7348, P < 0.0001). Immunoblocking against the CD146 receptor on ECFCs highlighted its notable role in ECFC homing with erythropoietin priming (ECFCEPO, 147% ± 14%, n = 4; ECFCEPO with antibody against CD146, 101% ± 12%, n = 4 [P < 0.05]). CONCLUSION: Priming with erythropoietin before cell transplantation is an efficient strategy to amplify the migratory and engraftment capacities of ECFCs and their beneficial impact on BBB disruption, apoptosis, and CBF.

Therapeutic benefit of a combined strategy using erythropoietin and endothelial progenitor cells after transient focal cerebral ischemia in rats.

OBJECTIVE: Many studies have demonstrated beneficial effects of either erythropoietin (EPO) or endothelial progenitor cell (EPC) treatment in cerebral ischemia. To improve post-ischemic tissue repair, we investigated the effect of systemic administration of endothelial colony-forming cells (ECFCs), considered as relevant endothelial progenitors due to their specific vasculogenic activity, in the presence or absence of EPO, on functional recovery, apoptosis, angiogenesis, and neurogenesis in a transient focal cerebral ischemia model in the adult rat. DESIGN: Experimental study. INTERVENTION: The rats were divided into four groups 24 hours after ischemia,, namely control, ECFCs, EPO, and ECFCs+EPO, and received a single intravenous injection of ECFCs (5 × 10(6) cells) and/or intraperitoneal administration of EPO (2500 UI/kg per day for 3 days). MEASUREMENT: Infarct volume, functional recovery, apoptosis, angiogenesis, and neurogenesis were assessed at different time points after ischemia. MAIN RESULTS: The combination of EPO and ECFCs was the only treatment that completely restored neurological function. The ECFCs+EPO treatment was also the most effective to decrease apoptosis and to increase angiogenesis and neurogenesis in the ischemic hemisphere compared to controls and to groups receiving ECFCs or EPO alone. CONCLUSION: These results suggest that EPO could act in a synergistic way with ECFCs to potentiate their therapeutic benefits.

[Coma following ethanol sclerotherapy]. / Coma éthylique secondaire à une sclérothérapie alcoolique.

INTRODUCTION: Simple serous renal cysts are an often asymptomatic benign disease, sometimes treated with ethanol sclerotherapy. We report a case of iatrogenic acute alcohol intoxication following percutaneous injection of alcohol into a renal cyst under local anesthesia. CASE: The percutaneous injection was guided by computed tomography. At the end of the procedure, the patient went into a coma due to alcohol intoxication: the cyst ruptured and ethanol was resorbed into the systemic circulation. DISCUSSION: Alcohol injection for sclerotherapy is used for several indications. This rare event has not previous been described, but should be known so that physicians can be prepared to manage it correctly.