Richard L. Applegate

Persistent sacral nerve root deficits after continuous spinal anaesthesia

Neurological deficits following spinal anaesthesia are rare. We report two cases of persistent sacral nerve root deficits after continuous spinal anaesthesia (CSA) performed with hyperbaric lidocaine through a lumbar microcatheter. In both cases the dose of 5% lidocaine (5.7 and 4.3 ml) was greater than usual. In the immediate postoperative period the constellation of neurological deficits included perianal hypaesthesia, lower extremity paresis, urinary retention, and difficult defaecation. Both patients have residual perianal hypaesthesia and difficult defaecation. In these cases, the high-dose requirements of local anaesthetic via microcatheter CSA with focal sensory block suggests nonuniform distribution of the hyperbaric lidocaine. Microcatheter CSA may convey a unique risk of maldistribution of the local anaesthetic solution and local neurotoxicity.RésuméLes déficits neurologiques après l’anaesthésie rachidienne sont rares. On rapporte deux cas de déficit persistant des racines nerveuses sacrées après une anesthésie rachidienne continue (CSA) avec la lidocaine hyperbare à travers un microcatheter lombaire. Dans les deux cas, la dose de lidocaine 5% (5,7 et 4,3 ml) était plus grande que d’habitude. Dans la période post-opératoire immédiate la constellation de déficits neurologiques ont compris une hypoasthésie périanale, une paresie des membres inférieurs, une rétention urinaire, et une défecation difficile. Les deux patients ont présenté une hypoasthésie périanale résiduelle et une difficulté à la défécation. Dans ces cas, des doses élevées d’anesthésiques locales requises à travers un microcatheter CSA avec blocage sensoriel focal suggère une distribution non uniforme de la lidocaine hyperbare. L’anesthésie rachidienne continue par microtheter peut présenter un risque unique de mauvaise distribution de la solution anesthésique locale et une neurotoxicité locale.

The accuracy of noninvasive and continuous total hemoglobin measurement by pulse CO-Oximetry in human subjects undergoing hemodilution.

BACKGROUND: Total hemoglobin (tHb) is one the most frequently ordered laboratory measurements. Pulse CO-Oximetry™ (Masimo Corp., Irvine, CA) is a multi-wavelength spectrophotometric method for noninvasive and continuous hemoglobin monitoring (SpHb). In this study, we evaluated the accuracy of SpHb compared with laboratory CO-Oximeter measurement of tHb from arterial blood samples in 20 healthy volunteer subjects undergoing hemodilution. METHODS: After enrollment, approximately 500 mL of blood was drawn from subjects through an arterial or venous catheter. Each subject then rapidly received crystalloid IV fluid to compensate for the decrease in intravascular volume and reduce the hemoglobin concentration. Subjects received a maximum of 30 mL/kg IV fluid. SpHb was continuously monitored and recorded, and serial arterial blood samples were taken during the procedure. SpHb accuracy was analyzed by pairing SpHb and tHb measurements after the arterial blood draw with the resulting tHb test result. Bias, precision, and the average root-mean-square error were calculated. RESULTS: One hundred sixty-five tHb measurements were collected. The average decrease in tHb during the blood removal and hemodilution procedure was 2.4 ± 0.8 g/dL (mean ± SD). The average difference between 335 paired measurements of SpHb and tHb was −0.15 g/dL, 1 SD of the difference was 0.92 g/dL, and the average root-mean-square difference was 0.94 g/dL. The difference between SpHb and tHb was <2.0 g/dL for 97% of the measurements. The difference was <1.5 g/dL for 97% of the measurements when tHb was <10 g/dL. CONCLUSIONS: Pulse CO-Oximetry–based SpHb measurement is accurate within 1.0 g/dL (1 SD) compared with laboratory CO-Oximeter tHb measurement in subjects undergoing hemodilution.

Dexmedetomidine for awake fiberoptic intubation in a parturient with spinal muscular atrophy type III for cesarean delivery

Spinal muscular atrophy in pregnancy is rare and poses multiple problems for the anesthesiologist. The effects of dexmedetomidine on a parturient with spinal muscular atrophy have not previously been reported. There are also no in vivo data on placental transfer of dexmedetomidine and its effects on a human neonate. We report the hemodynamic, respiratory and sedative effects of dexmedetomidine on a parturient and neonate when used for awake fiberoptic intubation before cesarean section. A 35-year-old, gravida 4 para 0 aborta 3, 41-kg parturient at 35 weeks of gestation with spinal muscular atrophy presented for cesarean section. Dexmedetomidine was administered intravenously, total dose 1.84 microg/kg over 38 minutes, followed by fiberoptic endotracheal intubation. Dexmedetomidine was then discontinued and general anesthesia was induced. The baby was delivered 68 minutes after the dexmedetomidine infusion was discontinued at which time blood samples were obtained for measurement of dexmedetomidine. During administration of dexmedetomidine, maternal heart rate, blood pressure and oxygen saturation remained stable. Apgar scores at 1 and 5 min were 6 and 8. The fetal concentration of dexmedetomidine (540 pg/mL) indicates significant placental transfer, but significant adverse neonatal effects were not observed. Dexmedetomidine alone provided adequate sedation for awake intubation without respiratory compromise in this patient.

Evaluation of pulse cooximetry in patients undergoing abdominal or pelvic surgery.

Background: Intraoperative transfusion decisions generally are guided by blood loss estimation and periodic invasive hemoglobin measurement. Continuous hemoglobin measurement by pulse cooximetry (pulse hemoglobin; Rainbow® SET Pulse CO-Oximeter, Masimo Corporation, Irvine, CA) has good agreement with laboratory hemoglobin in healthy volunteers and could aid transfusion decision-making. Because intraoperative physiology may alter performance of this device, this study investigated pulse hemoglobin during surgery. Methods: Ninety-one adult patients undergoing abdominal or pelvic surgery in which large blood loss was likely were studied. Time-matched pulse hemoglobin measurements were recorded for each intraoperative arterial hemoglobin measurement obtained. Agreement between measurements was assessed by average difference (mean ± SD, g/dl), linear regression, and multiple measures Bland-Altman analysis. Results: The average difference between 360 time-matched measurements (bias) was 0.50 ± 1.44 g/dl, with wider limits of agreement (−2.3 to 3.3 g/dl) than reported in healthy volunteers. The average difference between 269 paired sequential pulse and arterial hemoglobin changes was 0.10 ± 1.11 g/dl, with half between −0.6 and 0.7 g/dl of each other. The bias was larger in patients with blood loss of more than 1,000 ml; hemoglobin less than 9.0 g/dl; any intraoperative transfusion; or intraoperative decrease in arterial hemoglobin at the time of sampling ≥2 g/dl (all P < 0.001). The range of bias was narrower at deeper anesthesia (P < 0.001). Conclusions: Evaluation of the sensor and software version tested suggests that although pulse cooximetry may perform well in ambulatory subjects, in patients undergoing surgery in which large blood loss is likely, an invasive measurement should be used in transfusion decision-making.

Effect of Oncotic Pressure of Diaspirin Cross-Linked Hemoglobin (DCLHb Trademark) on Brain Injury After Temporary Focal Cerebral Ischemia in Rats

Previous studies have shown that diaspirin cross-linked hemoglobin (DCLHb Trademark, 10 g/dL) decreases cerebral ischemia and the resultant injury in a dose-dependent manner, requiring large volumes of DCLHb Trademark for maximum efficacy. We assessed the effect of a more concentrated (20 g/dL) and more hyperoncotic preparation of DCLHb Trademark on cerebral infarction volume. Immediately after middle cerebral artery occlusion, rats were randomized to one of the following groups: Control, hematocrit not manipulated; 10/Hb, hematocrit decreased to 30% with 10% DCLHb Trademark (oncotic pressure 43 mm Hg); 7.5/Alb, hematocrit decreased to 30% with 7.5% albumin (oncotic pressure 43 mm Hg); 20/Hb, the same dose of DCLHb Trademark (20%, oncotic pressure 129 mm Hg) as the 10/Hb group (half the volume); or 15/Alb, the same dose of albumin (15%, oncotic pressure 130 mm Hg) as the 7.5/Alb group (half the volume). After 90 min of ischemia, 72 h of reperfusion was allowed. Infarction volume (mm3, mean +/- SD) was less in the DCLHb Trademark groups (10/Hb = 79 +/- 17; 20/Hb = 51 +/- 14) than the oncotically matched albumin groups (7.5/Alb = 124 +/- 21; 15/Alb = 85 +/- 18) and the Control group (135 +/- 17) (P < 0.05). These data indicate that in this model of cerebral ischemia, DCLHb Trademark decreases ischemic brain injury more effectively than albumin, and that a hyperoncotic preparation of DCLHb Trademark is preferable. (Anesth Analg 1996;83:342-7)

Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on those recently reported methodological and mechanistic discoveries in the realm of ischemic conditioning. Due to the varied time differences of ischemic conditioning in different animal models and clinical trials, it is important to define optimal timing to achieve the best conditioning induced neuroprotection. This brings not only an opportunity in the treatment of stroke, but challenges as well, as data is just becoming available and the procedures are not yet optimized. The purpose of this review is to shed light on exploiting these ischemic conditioning modalities to protect the cerebrovascular system against diverse injuries and neurodegenerative disorders.

What's New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment.

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI.

Isoflurane posttreatment reduces brain injury after an intracerebral hemorrhagic stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating stroke subtype affecting 120,000 Americans annually. Of those affected, 40%to 50% will die within the first 30 days, whereas the survivors are left with a lifetime of neurobehavioral disabilities. Recently, it has been shown that volatile anesthetics such as isoflurane can reduce brain injury after an ischemic stroke. As a result, in this study, we investigated the effects of isoflurane as a posttreatment therapeutic modality in ICH-injured mice. Specifically, we investigated whether isoflurane posttreatment can preserve the structural integrity of the brain by reducing apoptotic damage and, in turn, improve functional outcome by amelioration of brain edema and neurobehavioral deficits. METHODS: Male CD1 mice (n = 53) were divided into the following groups: sham (n = 14), ICH (n = 14), ICH treated with 1.5% isoflurane posttreatment for 1 hour (n = 15), and ICH treated with 1.5% isoflurane posttreatment for 2 hours (n = 10). The blood injection ICH model was adapted; this involved extracting autologous blood from the mouse tail and injecting it directly into the right basal ganglia. One hour after surgery, treated mice were placed in a glass chamber maintained at 37°C and infused with 1.5% isoflurane for 1 or 2 hours. At 24 hours postinjury, mice were assessed for neurobehavioral deficits using the Modified Garcia Score and then killed and assessed for brain water content. Double immunofluorescent staining was performed using neuronal marker MAP-2 and TUNEL under a fluorescent microscope to assess for apoptosis. RESULTS: Our results indicated that after 1-hour 1.5% isoflurane posttreatment, there was a significant reduction in brain edema, a decrease in apoptotic cell death, and a significant improvement in neurobehavioral deficits. CONCLUSIONS: Our results suggest that isoflurane may be an effective posttreatment therapeutic option for ICH because of its ability to reduce structural damage and subsequently preserve functional integrity.

Accuracy of Cardiac Output Estimation With Biplane Transesophageal Echocardiography

To evaluate the accuracy of cardiac output measurements with biplane transesophageal Doppler echocardiography, we examined 26 sets of observations in 14 patients using thermodilution technique as the standard. A mitral inflow method by single-plane combined the time-velocity integral of mitral inflow at the mitral annulus with the area of mitral annulus, assuming it to be a circular shape, by use of either the four- or the two-chamber view. With both views, a mitral inflow method by biplane combined the average of time-velocity integral of mitral inflow from the four- and the two-chamber views with the area of mitral annulus, assuming it to be an ellipsoid shape. The correlation coefficients between thermodilution and single-plane method of cardiac output were 0.81 (SEE = 0.72 L/min) and 0.85 (SEE = 0.79 L/min) for the four- and the two-chamber views, respectively. The correlation coefficient with biplane method was 0.93 (SEE = 0.47 L/min). Thus, biplane transesophageal Doppler echocardiography can be used for more accurate estimation of cardiac output.

A systematic review of neuroprotective strategies after cardiac arrest: from bench to bedside (part II-comprehensive protection)

Neurocognitive deficits remain a significant source of morbidity in survivors of cardiac arrest. We conducted a literature review of treatment protocols designed to evaluate neurologic outcome and survival following global cerebral ischemia associated with cardiac arrest. The search was limited to investigational therapies that were implemented either during cardiopulmonary resuscitation or after return of spontaneous circulation in studies that included assessment of impact on neurologic outcome. Given that complex pathophysiology underlies global brain hypoxic ischemia following cardiac arrest, neuroprotective strategies targeting multiple stages of neuropathologic cascades should promise to improve survival and neurologic outcomes in cardiac arrest victims. In Part II of this review, we discuss several approaches that can provide comprehensive protection against global brain injury associated with cardiac arrest, by modulating multiple targets of neuropathologic cascades. Pharmaceutical approaches include adenosine and growth factors/hormones including brain-derived neurotrophic factor, insulin-like growth factor-1 and glycine-proline-glutamate, granulocyte colony stimulating factor and estrogen. Preclinical studies of these showed some benefit but were inconclusive in models of global brain injury involving systemic ischemia. Several medical gases that can mediate neuroprotection have been evaluated in experimental settings. These include hydrogen sulfide, hyperbaric oxygen and molecular hydrogen. Hyperbaric oxygen and molecular hydrogen showed promising results; however, further investigation is required prior to clinical application of these agents in cardiac arrest patients.