Rotational thromboelastometry-guided blood product management in major spine surgery.

OBJECT Major spinal surgery in adult patients is often associated with significant intraoperative blood loss. Rotational thromboelastometry (ROTEM) is a functional viscoelastometric method for real-time hemostasis testing. In this study, the authors sought to characterize the coagulation abnormalities encountered in spine surgery and determine whether a ROTEM-guided, protocol-based approach to transfusion reduced blood loss and blood product use and cost. METHODS A hospital database was used to identify patients who had undergone adult deformity correction spine surgery with ROTEM-guided therapy. All patients who received ROTEM-guided therapy (ROTEM group) were matched with historical cohorts whose coagulation status had not been evaluated with ROTEM but who were treated using a conventional clinical and point-of-care laboratory approach to transfusion (Conventional group). Both groups were subdivided into 2 groups based on whether they had received intraoperative tranexamic acid (TXA), the only coagulation-modifying medication administered intraoperatively during the study period. In the ROTEM group, 26 patients received TXA (ROTEM-TXA group) and 24 did not (ROTEM-nonTXA group). Demographic, surgical, laboratory, and perioperative transfusion data were recorded. Data were analyzed by rank permutation test, adapted for the 1:2 ROTEM-to-Conventional matching structure, with p < 0.05 considered significant. RESULTS Comparison of the 2 groups in which TXA was used showed significantly less fresh-frozen plasma (FFP) use in the ROTEM-TXA group than in the Conventional-TXA group (median 0 units [range 0-4 units] vs 2.5 units [range 0-13 units], p < 0.0002) but significantly more cryoprecipitate use (median 1 unit [range 0-4 units] in the ROTEM-TXA group vs 0 units [range 0-2 units] in the Conventional-TXA group, p < 0.05), with a nonsignificant reduction in blood loss (median 2.6 L [range 0.9-5.4 L] in the ROTEM-TXA group vs 2.9 L [0.7-7.0 L] in the Conventional-TXA group, p = 0.21). In the 2 groups in which TXA was not used, the ROTEM-nonTXA group showed significantly less blood loss than the Conventional-nonTXA group (median 1 L [range 0.2-6.0 L] vs 1.5 L [range 1.0-4.5 L], p = 0.0005), with a trend toward less transfusion of packed red blood cells (pRBC) (median 0 units [range 0-4 units] vs 1 unit [range 0-9 units], p = 0.09]. Cryoprecipitate use was increased and FFP use decreased in response to ROTEM analysis identifying hypofibrinogenemia as a major contributor to ongoing coagulopathy. CONCLUSIONS In major spine surgery, ROTEM-guided transfusion allows for standardization of transfusion practices and early identification and treatment of hypofibrinogenemia. Hypofibrinogenemia is an important cause of the coagulopathy encountered during these procedures and aggressive management of this complication is associated with less intraoperative blood loss, reduced transfusion requirements, and decreased transfusion-related cost.

Safety of an alkalinizing buffer designed for inhaled medications in humans.

BACKGROUND: Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease. METHODS: This work includes 2 open-label safety studies. The healthy controls were part of a phase 1 safety study of multiple inhalations of low-dose alkaline glycine buffer; nebulized saline was used as a comparator in 8 of the healthy controls. Subsequently, a phase 2 study in subjects with stable obstructive airway disease was completed using a single nebulized higher-dose strategy of the alkaline inhalation. We studied 20 non-smoking adults (10 healthy controls and 10 subjects with obstructive airway disease), both at baseline and after inhalation of alkaline buffer. We used spirometry and vital signs as markers of clinical safety. We used changes in fraction of exhaled nitric oxide (NO) and exhaled breath condensate (EBC) pH as surrogate markers of airway pH modification. RESULTS: Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway alkalinization was confirmed by a median increase in EBC pH of 0.235 pH units (IQR 0.56-0.03, P = .03) in subjects after inhalation of the higher-dose alkaline buffer (2.5 mL of 100 mmol/L glycine). CONCLUSIONS: Alkalinization of airway lining fluid is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.

Current approach on spinal cord monitoring: the point of view of the neurologist, the anesthesiologist and the spine surgeon.

Optimal outcome in spine surgery is dependent of the coordination of efforts by the surgeon, anesthesiologist, and neurophysiologist. This is perhaps best illustrated by the rising use of intraoperative spinal cord monitoring for complex spine surgery. The challenges presented by neurophysiologic monitoring, in particular the use of somatosensory and motor evoked potentials, requires an understanding by each member for the team of the proposed operative procedure as well as an ability to help differentiate clinically important signal changes from false positive changes. Surgical, anesthetic, and monitoring issues need to be addressed when relying on this form of monitoring to reduce the potential of negative outcomes in spine surgery. This article provides a practical overview from the perspective of the neurophysiologist, the anesthesiologist, and the surgeon on the requirements which must be understood by these participants in order to successfully contribute to a positive outcome when a patient is undergoing complex spine surgery.

Exhaled-breath condensate pH can be safely and continuously monitored in mechanically ventilated patients.

BACKGROUND: Airway inflammation in acute and chronic respiratory diseases is characterized in part by abnormal pH in airway-lining fluid. The pH of exhaled-breath condensate (EBC) is low (acidic) in various pulmonary inflammatory diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, pneumonia, and acute respiratory distress syndrome. Because the time course of pH changes in the airway is not yet clear, we aimed to develop a method for frequent and intensive EBC pH data collection in mechanically ventilated patients. METHODS: We examined the collection, gas-standardizing (CO2 removal), and continuous monitoring of pH of EBC from the expiratory port of a Servo-i ventilator with mechanically ventilated patients. We developed a condensing device that attaches to the exhaust port and is chilled by an electric cooling system. We built a 2-chamber gas-standardization and pH-measuring device that attaches to the condensing system and records pH every 6 s. After safety testing, we enrolled mechanically ventilated patients (with diverse reasons for requiring ventilatory support) for up to 96 h of continuous EBC pH condensimetry. RESULTS: The pressure, volume, and flow of the ventilator attached to a test lung were unchanged by application of the condensimeter, at various flows (2-120 L/min) and ventilator settings. We monitored 19 pediatric patients for 6-96 h. The pH of the accumulated EBC in the storage container correlated with the geometric mean of all the pH data points from the condensimeter during the recording period (r2 = -0.95, p < 0.001), which internally validated that the condensimetry system provides accurate, well gas-standardized readings for up to 96 h. The EBC pH values were similar to published reports of single samples. The EBC pH became more acidic during clinical deterioration and normalized with recovery. CONCLUSION: Continuous monitoring of EBC pH from the ventilator exhaust port is safely achievable and reliably provides data that may become useful in monitoring critically ill patients.

The soluble guanylyl cyclase inhibitor ODQ, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, dose-dependently reduces the threshold for isoflurane anesthesia in rats.

Nitric oxide (NO), a cell messenger for activating soluble guanylyl cyclase, is produced by activation of the enzyme NO synthase (NOS) in a wide variety of tissues, including the central nervous system. We have previously demonstrated that inhibition of NOS decreased the minimum alveolar anesthesia concentration (MAC) for isoflurane anesthesia. Moving more distally in the NOS-guanylyl cyclase signaling pathway, we investigated the effects of the specific soluble guanylyl cyclase inhibitor ODQ, 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one, on anesthetic requirements. The effect of ODQ on the MAC of isoflurane anesthesia was investigated in Sprague-Dawley rats while concurrently monitoring the their arterial blood pressure and heart rate. After determining control MAC, ODQ 20-500 mg/kg was administered intraperitoneally 30 min before re-determining MAC in the presence of the soluble guanylyl cyclase inhibitor. In one series, the effect of 250 mg/kg of ODQ on neuronal cyclase guanosine monophosphate production was determined by microdialysis. ODQ produced a statistically significant, dose-dependent decrease from isoflurane control MAC (maximal effect 52.4% +/- 2.7%). No ceiling effect was observed over the dose-range studied. This reduction in isoflurane MAC was not accompanied by changes in either heart rate or blood pressure. Inhibition of the NOS-guanylyl cyclase signaling pathway decreased the MAC for isoflurane, which suggests that inhibition of this pathway may play a role in the anesthetic state. The MAC reduction by the soluble guanylyl cyclase inhibitor ODQ was devoid of any significant hemodynamic effects. The current findings, along with the previous observations that structurally distinct NOS inhibitors and the nonspecific soluble guanylyl cyclase inhibitor methylene blue decrease the MAC for volatile anesthetics, support that this is an effect specific to the NOS-guanylyl cyclase signaling pathway.

Safety and efficacy of ERCP in pregnancy.

BACKGROUND: Choledocholithiasis during pregnancy increases the risk of morbidity and mortality for both fetus and mother because of cholangitis and pancreatitis. ERCP has been advocated as safe and effective in pregnant women, but fetal radiation exposure is not routinely monitored. The aim of this study was to record fetal exposure to ionizing radiation during ERCP and to assess outcome. METHODS: Seventeen ERCPs were performed in pregnant women between January 1995 and August 2003. Techniques to minimize fluoroscopy were used, and fluoroscopy times were recorded. Thermoluminescent dosimeters affixed to the skin of the mother were used to estimate fetal radiation exposure. OBSERVATIONS: Mean gestational age was 18.6 (8.9) weeks (range 5-33 weeks). Mean fluoroscopy time was 14 (13) seconds (range 1-48 seconds). Estimated fetal radiation exposure was 40 (46) mrad (range 1-180 mrad). There was a correlation between fluoroscopy time and radiation exposure, but there was a wide range of radiation exposure for individual fluoroscopy times. Complications included post-sphincterotomy bleeding in one patient (controlled by hemoclip placement) and post-ERCP pancreatitis in one patient that necessitated 3 days of hospitalization. Two women developed third-trimester preeclampsia, and labor was induced in both. Thirteen of the 15 patients who delivered were contacted and they confirmed that their child was in good health. CONCLUSIONS: ERCP with modified techniques is safe during pregnancy. Dosimetry should be routinely recorded.

Design, synthesis, and evaluation of analogues of 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide as orally available general anesthetics.

We have recently discovered a novel class of compounds that have oral general anesthetic activity, potent anticonvulsant activity, and minimal hemodynamic effects. The 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide (1) demonstrated potent ability to reduce the minimum alveolar concentration (MAC) of isoflurane, with no effects on heart rate or blood pressure at therapeutic concentrations. Analogue 1 also had potent oral anticonvulsant activity against maximal electroshock (MES) and subcutaneous metrazol (scMET) models with a therapeutic index of 10 for MES activity. In this study, we further synthesized nine new racemic analogues and evaluated these compounds for effects on isoflurane MAC reduction and blood pressure. Preliminary data demonstrate potent reduction in the isoflurane MAC for two new compounds. Current mechanistic studies were unrevealing for effects on voltage-gated ion channels as a putative mechanism. Liposomal partitioning studies using (19)F NMR reveal that the aromatic region partitions into the core of the lipid. This partitioning correlated with general anesthetic activity of this class of compounds. Further, compound 1 was used at a concentration of 1 mM and slightly enhanced GABA(A) current in hippocampal neurons at 10 microM. Altogether, 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide exhibited excellent oral general anesthetic activity and appears devoid of significant side effects (i.e., alterations in blood pressure or heart rate).