Hypotension and hypocapnia during general anesthesia in piglets: study of S100b as an acute biomarker for cerebral tissue injury

BACKGROUND Hypotension and/or hypocapnia might increase general anesthesia (GA)-related neuromorbidity in infants, but safe levels of perioperative blood pressure are poorly defined. Serum protein S100b has been used as screening, monitoring, and prediction tool in the management of patients with traumatic brain injury. Using an animal model, we investigated serum S100b as an acute biomarker of cerebral hypoperfusion and cerebral cell dysfunction during hypotension, hypocapnia, or combined hypotension/hypocapnia during GA. METHODS Fifty-seven sevoflurane-midazolam anesthetized piglets aged 4 to 6 weeks were randomly allocated to control (n=9), hypotension (n=18), hypocapnia (n=20), or combined hypotension and hypocapnia (n=10). Hypotension (target mean arterial blood pressure: 35 to 38 or 27 to 30 mm Hg) was induced by blood withdrawal and nitroprusside infusion, and hypocapnia by hyperventilation (target PaCO2: 28 to 30 and 23 to 25 mm Hg). Serum S100b and albumin were measured at baseline, before and 60 minutes after the interventions, and following 60-minute recovery. RESULTS Serum S100b concentrations decreased over time (P=0.001), but there was no difference in S100b between control piglets and those exposed to hypotension, hypocapnea, or a combination of the both (P=0.105). Albumin decreased in all 4 groups (P=0.001). CONCLUSION S100b did not increase following 60 minutes of systemic hypotension and/or hypocapnia during GA in piglets. In this setting, the use of S100b as a biomarker of cerebral cell tissue dysfunction cannot be supported

Impact of incorrect filling of citrate blood sampling tubes on thromboelastometry

BACKGROUND ROTEM(®) test results can be affected by the citrate to blood ratio in the tested sample. Overfilling or underfilling specimen tubes can change this ratio. OBJECTIVES The aim of this study was to determine the impact of under- and overfilling citrate test tubes on ROTEM(®) EXTEM measurements. RESULTS Overall repeated measures ANOVA demonstrated significant differences of CT (p = 0.004), CFT (p = 0.005), A5 (p = 0.001), A10 (p <0.001), and MCF (p < 0.001). Pairwise comparison revealed that underfilling significantly altered the results of those parameters reflecting functional clot firmness (A5, A10, and MCF), while overfilling led to a prolongation of the CT results only. No differences were observed for alpha angle and maximum lysis. CONCLUSION Both underfilling and overfilling specimen tubes have significant influence on the results of the ROTEM(®) EXTEM test, although the small observed bias is likely of limited clinical relevance. However, it seems prudent to limit the maximum allowed difference in filling to less than ± 10%. All ROTEM(®) operators should be aware of this pre-analytical variable

Impact of catecholamines in cardiac arrest due to acute asphyxia - a study in piglets

BACKGROUND Early intravenous epinephrine administration may help to achieve return of spontaneous circulation in cardiac arrest (CA). However, venous access can be challenging in small children. This study investigates the effect of intravenous and intramuscular epinephrine in treatment of asphyxial CA. METHODS Twenty-eight, 2-5-weeks-old, anesthetized piglets were asphyxiated by ventilation withdrawal. CA was untreated for 8 min, followed by 2 min of basic life support. Following this, epinephrine iv (10 μg•kg(-1) , group IV), epinephrine im (100 μg•kg(-1) , group IM), or normal saline (group NS) were administered. Further doses of epinephrine were given in group IV every 4 min, in group IM after 10 min if required. After twenty-two minutes of CA, iv epinephrine was given to all animals still in CA. Outcome measures were survival and epinephrine plasma concentrations. RESULTS Ten animals regained spontaneous circulation after 2 min of basic life support. Therefore, no drug treatment was administered (drop out). Resuscitation was effective in 2 pigs of group IM (n = 6), in 6 of group NS (n = 8) and in all of group IV (n = 4). Nonsurvivors had higher epinephrine (P < 0.01) and norepinephrine (P < 0.01) plasma concentrations prior to start of resuscitation. Median increase in epinephrine plasma concentration from T0 to T5 was 138, 134, and 29 nm in group IV, IM, and NS, respectively. CONCLUSIONS Intravenous and intramuscular administered epinephrine led to similar increase in plasma concentrations during resuscitation of asphyxial CA without hemodynamic or survival benefit. High endogenous epinephrine and norepinephrine plasma concentrations were negative predictors for survival

Intravenous versus intramuscular epinephrine administration during cardiopulmonary resuscitation - a pilot study in piglets

BACKGROUND: Early epinephrine administration in cardiac arrest seems to be advantageous to achieve return of spontaneous circulation (ROSC). Because intravenous (i.v.) or intraosseous access is not always immediately available, this study compares efficacy of early intramuscular (i.m.) epinephrine administration with early and delayed i.v. epinephrine injection in an animal cardiac arrest model. METHODS: Piglets anesthetized with sevoflurane were intoxicated by an i.v. ropivacaine infusion until circulatory arrest. After 1 min basic life support (chest compression and ventilation), epinephrine i.v. (10 μg·kg(-1), group IV) or epinephrine i.m. (100 μg·kg(-1), group IM) or normal saline (group NS) was applied. Further doses of epinephrine were given in group IV every 4 min and in group IM after 10 min if required. Twenty-one minutes after circulatory arrest, i.v. epinephrine - as necessary - was given to all animals. Thus, group NS represents late epinephrine administration. Outcomes were survival and time to ROSC. RESULTS: Twenty-four pigs aged 19.5 (median, interquartile range 16-22) days, weighing 5.4 (5.0-5.7) kg were investigated. Total amount of ropivacaine administered was 8.9 (8.1-10.1) mg·kg(-1). Cardiac rhythm before starting CPR was pulseless electric activity and asystole in 15 and 9 pigs, respectively. Eight, seven, and four pigs survived in group IV, IM, and NS. Focusing on surviving animals, time to ROSC was 2, 4 and 19.5 min in group IV, IM, and NS. CONCLUSIONS: Early i.m. epinephrine provided similar survival compared with early i.v. epinephrine and was superior to delayed epinephrine administration in resuscitation of ropivacaine-induced cardiac arrest in piglets

Effect of Lanz Pressure Regulating Valve on Self-sealing Mechanism and Air Leakage Across the Tracheal Tube Cuffs in a Benchtop Model

Background: The aim of the present study was to investigate the effect of the Lanz system on air sealing by self-inflation in high volume-low pressure (HVLP) tube cuffs. Methods: In vitro tracheal air sealing was studied in HVLP tracheal tube cuffs (internal diameter [ID] 8.0 mm) made from polyurethane ([PU] Seal Guard tracheal tube, Covidien, Athlone, Ireland) and from polyvinylchloride ([PVC] HiLo tracheal tube, Covidien) with and without Lanz pressure regulating valve. Tube cuffs were placed in a vertical 22 mm ID artificial trachea and inflated to 5, 10, 15, 20, 25, or 30 cm H(2)O cuff pressures. Pressure control ventilation with peak inspiratory pressures (PIPs) of 20 or 25 cm H(2)O was applied and air leakage was assessed spirometrically as the ratio of expiratory to inspiratory tidal volumes. Nonparametric Mann-Whitney test was applied to compare the air leakage with and without Lanz system for both cuff types at each cuff pressure and PIP (P < .05). Results: The PVC tube cuffs with Lanz system resulted in significant air leakage at both 20 and 25 cm H(2)O PIP as compared to those without the Lanz system, especially at cuff pressures lower than the preset PIP (P < .05). Although PU tube cuffs with Lanz system showed reduced air sealing when compared with cuffs without Lanz, the difference was not statistically significant. Conclusion: Cuff pressure compensation with the Lanz system during cyclic respiratory pressure changes interferes with the self-sealing mechanism in HVLP tube cuffs at cuff pressures lower than PIP level. This results in larger air leak across tube cuffs particularly in tube cuffs made from PVC

Improvements in patient blood management for pediatric craniosynostosis surgery using a ROTEM(®) -assisted strategy - feasibility and costs

BACKGROUND: Moderate to severe intraoperative bleeding and the presence of acquired coagulopathy remain serious problems in the management of major pediatric craniosynostosis surgery. After implementation of a ROTEM(®) -assisted patient blood management (PBM) strategy, using primarily purified coagulation factor concentrates, feasibility and costs of this new regimen were analyzed. METHODS: Retrospective analysis of all consecutive children who underwent primary elective major craniofacial surgery for craniosynostosis repair was carried out at the Children's University Hospital, Zurich, between 2007 and 2013. Laboratory workup and transfusion requirements were compared. RESULTS: A total of 47 children (36 in the historic group and 11 after implementation of PBM) were analyzed. Although all patients in this study needed transfusion of red blood cell concentrates, there was a total avoidance of perioperative transfusion of fresh frozen plasma and a reduction in transfused platelets (one of nine children vs nine of 36 children in the historic group) after implementation of the PBM strategy. Based on a predefined ROTEM(®) threshold in the PBM group (FibTEM MCF <8 mm), administration of fibrinogen concentrate was necessary in all of these children. The mean total costs per patient consisting of transfused allogeneic blood products and coagulation factor concentrates were reduced by 17.1% after implementation of PBM (1071.82 EUR per patient before vs 888.93 EUR after implementation). CONCLUSIONS: The implementation of a ROTEM(®) -assisted PBM is feasible and is associated with a considerable reduction in intraoperative transfusion requirements and thereby a decrease in transfusion-related direct costs

Effects of hypothermia and hypothermia combined with hypocapnia on cerebral tissue oxygenation in piglets

Background: Hypothermia and its combination with hypocapnia are frequently associated with anesthesia. Aims: The goal was to investigate the effects of hypothermia and hypothermia combined with hypocapnia (hypothermia-hypocapnia) on cerebral tissue oxygenation in anesthetized piglets. Methods: Twenty anesthetized piglets were randomly allocated to hypothermia (n = 10) or hypothermia-hypocapnia (n = 10). Cerebral monitoring comprised a tissue oxygen partial pressure (PtO2 ), a laser Doppler probe, and a near-infrared spectroscopy sensor, measuring regional oxygen saturation (rSO2 ). After baseline recordings, hypothermia (35.5-36.0°C) with or without hypocapnia (target PaCO2 : 28-30 mm Hg) was induced. Once treatment goals were achieved (Tr0), they were maintained for 30 minutes (Tr30). Results: No changes in PtO2 but a significant increase in rSO2 (Tr0 (mean difference 8.9[95% CI for difference3.99 to 13.81], P < .001); Tr30 (10.8[6.20 to 15.40], P < .001)) were detected during hypothermia. With hypothermia-hypocapnia, a decrease in PtO2 (Tr0 (-3.2[-6.01 to -0.39], P = .021; Tr30 (-3.3[-5.8 to -0.80], P = .006)) and no significant changes in rSO2 occurred. Cerebral blood flow decreased significantly from baseline to Tr0 independently of treatment (-0.89[-0.18 to -0.002], P = .042), but this was more consistently observed with hypothermia-hypocapnia. Conclusions: The hypothermia-induced reduction in oxygen delivery was compensated by lowered metabolic demand. However, hypothermia was not able to compensate for an additional reduction in oxygen delivery caused by simultaneous hypocapnia. This resulted in a PtO2 drop, which was not reflected by a downshift in rSO2

Effects of moderate and severe hypocapnia on intracerebral perfusion and brain tissue oxygenation in piglets.

BACKGROUND: Hypocapnia is a common alteration during anesthesia in neonates. AIM: To investigate the effects of hypocapnia and hypocapnia combined with hypotension (HCT) on cerebral perfusion and tissue oxygenation in anesthetized piglets. METHOD: Thirty anesthetized piglets were randomly allocated to groups: moderate hypocapnia (mHC), severe hypocapnia (sHC), and HCT. Cerebral monitoring comprised a tissue oxygen partial pressure and a laser Doppler probe inserted into the brain tissue as well as a near-infrared spectroscopy (NIRS) sensor placed on the skin, measuring regional oxygen saturation. Hypocapnia was induced by hyperventilation (target PaCO$_{2}$ mHC: 3.7-4; sHC: 3.1-3.3 kPa) and hypotension by blood withdrawal and nitroprusside infusion (mean blood pressure: 35-38 mm Hg). Data were analyzed at baseline, during (Tr20, Tr40, Tr60) and after (Post20, Post40, Post60) treatment. RESULTS: Compared to baseline, tissue oxygen partial pressure decreased significantly and equally during all treatments (mean [SD] at baseline: mHC 35.7 [32.45]; sHC: 28.1 [20.24]; HCT 25.4 [10.3] and at Tr60: mHC: 29.9 [27.36]; sHC: 22.2 [18.37]; HCT: 18.4 [9.5] mm Hg). Decreased laser Doppler flow was detected with all treatments at Tr20 (mHC: 0.9 [0.18]; sHC: 0.88 [0.15]; HCT: 0.97 [0.13] proportion from baseline). Independently of group, regional oxygen saturation varied only after reverting and not during treatment. Blood lactate, pH, HCO$_{3}$$^{-}$ , and PaO$_{2}$ increased during treatment with no differences between groups. CONCLUSION: This animal model revealed reduced cerebral blood flow and brain tissue oxygenation during hypocapnia without detectable changes in regional oxygen saturation as measured by NIRS. Changes occurred as early as during moderate hypocapnia

Comparison of conventional ROTEM® cups and pins to the ROTEM® cup and pin mini measuring cells (MiniCup)

BACKGROUND: Thromboelastometry (ROTEM®) is a well-established measurement to guide perioperative coagulation management. Recently, an enhancement for low volume specimens using cup and pin mini measuring cells (MiniCup) was invented for scientific non-clinical use. The MiniCup measuring cells allow testing with half of the blood volume required to run a test as compared to the conventional ROTEM® cup and pin (150 μL vs. 300 μL per assay). OBJECTIVES: The aim of this prospective study was to compare ROTEM® results using conventional cups and pins to the results of the MiniCup measuring cells. METHODS: Blood samples drawn during major pediatric surgery were analyzed using the conventional ROTEM® and the MiniCup system to compare parameters from the EXTEM, INTEM and FIBTEM assays. RESULTS: Citrated blood samples (n = 120) from 70 pediatric patients were analyzed. Results of the MiniCup cells were considerably different than the conventional ROTEM® cups and pins measurements. The MiniCup results show less clot firmness and demonstrate higher variability in the parameters reflecting the kinetics of clot building. CONCLUSION: The MiniCup measuring cells may offer advantages in pediatric care or research facilities, but specific reference ranges need to be established first, and adequate reproducibility must be determined by further studies before clinical use can be recommended