Trauma-related preventable death; data analysis and panel review at a level 1 trauma centre in Amsterdam, the Netherlands.

PURPOSE: Trauma-related death is used as a parameter to evaluate the quality of trauma care and identify cases in which mortality could have been prevented under optimal trauma care conditions. The aim of this study was to identify trauma-related preventable death (TRPD) within our institute by an external expert panel and to evaluate inter-panel reliability. METHODS: Trauma-related deaths between the 1st of January 2020 and the 1st of February 2022 at the Amsterdam University Medical Centre were identified. The severely injured patients (injury severity score ≥ 16) were enrolled for preventability analysis by an external multidisciplinary panel, consisting of a trauma surgeon, anaesthesiologist, emergency physician, neurosurgeon, and forensic physician. Case descriptions were provided, and panellists were asked to classify deaths as non-preventable, potentially preventable, and preventable. Agreements between the five observers were assessed by Fleiss kappa statistics. RESULTS: In total 95 trauma-related deaths were identified. Of which 36 fatalities were included for analysis, the mean age was 55.3 years (± 24.5), 69.4% were male and 88.9% suffered blunt trauma. The mean injury severity score was 35.3 (± 15.3). Interobserver agreement within the external panel was moderate for survivability (Fleiss kappa 0.474) but low for categorical preventable death classification (Fleiss kappa 0.298). Most of the disagreements were between non-preventable or potentially preventable with care that could have been improved. CONCLUSION: Multidisciplinary panel review has a moderate inter-observer agreement regarding survivability and low agreement regarding categorical preventable death classification. A valid definition and classification of TRPD is required to improve inter-observer agreement and quality of trauma care.

Characteristics of helicopter emergency medical services (HEMS) dispatch cancellations during a six-year period in a Dutch HEMS region.

BACKGROUND: For decades, Helicopter Emergency Medical Services (HEMS) contribute greatly to prehospital patient care by performing advanced medical interventions on-scene. Unnecessary dispatches, resulting in cancellations, cause these vital resources to be temporarily unavailable and generate additional costs. A previous study showed a cancellation rate of 43.5% in our trauma region. However, little recent data about cancellation rates and reasons exist, despite revision of dispatch protocols. This study examines the current cancellation rate in our trauma region over a six-year period. Additionally, cancellation reasons are evaluated per type of dispatch and initial incident report, upon which HEMS is dispatched. METHODS: This retrospective study analyzed the data of the Dutch HEMS Lifeliner 1 (North-West region of the Netherlands, covering a population of 5 million inhabitants), analyzing all subsequent cases between April 1st 2013 and April 1st 2019. Patient characteristics, type of dispatch (primary; based on dispatcher criteria versus secondary, as judged by the first ambulance team on site), initial incident report received by the EMS dispatch center, and information regarding day- or nighttime dispatches were collected. In case of cancellation, cancel rate and reason per type of dispatch and initial incident report were assessed. RESULTS: In total, 18,638 dispatches were included. HEMS was canceled in 54.5% (95% CI 53.8-55.3%) of cases. The majority of canceled dispatches (76.1%) were canceled because respiratory, hemodynamic, and neurologic parameters were stable. Dispatches simultaneously activated with EMS (primary dispatch) were canceled in 58.3%, compared to 15.1% when HEMS assistance was requested by EMS based on their findings on-scene (secondary dispatch). A cancellation rate of 54.6% was found in trauma related dispatches (n = 12,148), compared to 52.2% in non-trauma related dispatches (n = 5378). Higher cancellation rates exceeding 60% were observed in the less common dispatch categories, e.g., anaphylaxis (66.3%), unknown incident report (66.0%), assault with a blunt object (64.1%), obstetrics (62.8%), and submersion (61.9%). CONCLUSION: HEMS cancellations are increased, compared to previous research in our region. Yet, the cancellations are acceptable as the effect on HEMS' unavailbility remains minimized. Focus should be on identifying the patient in need of HEMS care while maintaining overtriage rates low. Continuous evaluation of HEMS triage is important, and dispatch criteria should be adjusted if necessary.

Prehospital fluid administration in patients with severe traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: Prehospital management of severe traumatic brain injury (TBI) focuses on preventing secondary brain injury. Therefore, hypotension should be prevented, or if present, should be promptly treated in order to maintain optimal cerebral perfusion pressure. Fluid resuscitation is a traditional mainstay in the prehospital treatment of hypotension, however, the choice of fluid type that is to be administered in the prehospital setting is the subject of an on-going debate. This systematic review and meta-analysis was therefore performed to assess the effect of different fluid types on outcome in patients with severe TBI. METHODS: PubMed, Embase and Web of Science were searched for articles up to March 2020. Studies comparing two or more prehospital administered fluid types with suspected or confirmed severe TBI were deemed eligible for inclusion. Studied outcomes were mortality and (extended) Glasgow Outcome Scale (GOS). The meta-analysis tested for differences in survival between hypertonic saline (HTS) and normotonic crystalloids (i.e. normal saline or Lactated Ringer's) and between hypertonic saline with dextran (HSD) and normotonic crystalloids. The systematic review is registered in the PROSPERO register with number CRD42020140423. RESULTS: This literature search yielded a total of 519 articles, of which 12 were included in the systematic review and 6 were included in the meta-analysis. Eleven studies found no statistically significant difference in survival between patients treated with different fluid types (e.g. normal saline and hypertonic saline). All studies assessing neurological outcome, measured through (extended) GOS, found no statistically significant difference between different fluid types. Meta-analysis showed no better survival for patients treated with HSD, when compared to normotonic crystalloids (overall RR 0.99, 95% CI 0.93-1.06). Moreover, HTS compared to normotonic crystalloids does not result in a better survival (overall RR 1.04, 95% CI 0.97-1.12). CONCLUSIONS: This systematic review and meta-analysis did not demonstrate a survival or neurological benefit for one specific fluid type administered in the prehospital setting.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

Reduction of vascular leakage by imatinib is associated with preserved microcirculatory perfusion and reduced renal injury markers in a rat model of cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass during cardiac surgery leads to impaired microcirculatory perfusion. We hypothesized that vascular leakage is an important contributor to microcirculatory dysfunction. Imatinib, a tyrosine kinase inhibitor, has been shown to reduce vascular leakage in septic mice. We investigated whether prevention of vascular leakage using imatinib preserves microcirculatory perfusion and reduces organ injury markers in a rat model of cardiopulmonary bypass. METHODS: Male Wistar rats underwent cardiopulmonary bypass after treatment with imatinib or vehicle (n=8 per group). Cremaster muscle microcirculatory perfusion and quadriceps microvascular oxygen saturation were measured using intravital microscopy and reflectance spectroscopy. Evans Blue extravasation was determined in separate experiments. Organ injury markers were determined in plasma, intestine, kidney, and lungs. RESULTS: The onset of cardiopulmonary bypass decreased the number of perfused microvessels by 40% in the control group [9.4 (8.6-10.6) to 5.7 (4.8-6.2) per microscope field; P<0.001 vs baseline], whereas this reduction was not seen in the imatinib group. In the control group, the number of perfused capillaries remained low throughout the experiment, whilst perfusion remained normal after imatinib administration. Microvascular oxygen saturation was less impaired after imatinib treatment compared with controls. Imatinib reduced vascular leakage and decreased fluid resuscitation compared with control [3 (3-6) vs 12 ml (7-16); P=0.024]. Plasma neutrophil-gelatinase-associated-lipocalin concentrations were reduced by imatinib. CONCLUSIONS: Prevention of endothelial barrier dysfunction using imatinib preserved microcirculatory perfusion and oxygenation during and after cardiopulmonary bypass. Moreover, imatinib-induced protection of endothelial barrier integrity reduced fluid-resuscitation requirements and attenuated renal and pulmonary injury markers.

Application of current guidelines for chest compression depth on different surfaces and using feedback devices: a randomized cross-over study.

BACKGROUND: Current cardiopulmonary resuscitation (CPR)-guidelines recommend an increased chest compression depth and rate compared to previous guidelines, and the use of automatic feedback devices is encouraged. However, it is unclear whether this compression depth can be maintained at an increased frequency. Moreover, the underlying surface may influence accuracy of feedback devices. We investigated compression depths over time and evaluated the accuracy of a feedback device on different surfaces. METHODS: Twenty-four volunteers performed four two-minute blocks of CPR targeting at current guideline recommendations on different surfaces (floor, mattress, 2 backboards) on a patient simulator. Participants rested for 2 minutes between blocks. Influences of time and different surfaces on chest compression depth (ANOVA, mean [95% CI]) and accuracy of a feedback device to determine compression depth (Bland-Altman) were assessed. RESULTS: Mean compression depth did not reach recommended depth and decreased over time during all blocks (first block: from 42 mm [39-46 mm] to 39 mm [37-42 mm]). A two-minute resting period was insufficient to restore compression depth to baseline. No differences in compression depth were observed on different surfaces. The feedback device slightly underestimated compression depth on the floor (bias -3.9 mm), but markedly overestimated on the mattress (bias +12.6 mm). This overestimation was eliminated after correcting compression depth by a second sensor between manikin and mattress. CONCLUSION: Strategies are needed to improve chest compression depth, and more than two providers should alternate with chest compressions. The underlying surface does not necessarily adversely affect CPR performance but influences accuracy of feedback devices. Accuracy is improved by a second, posterior, sensor.

Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

Tissue hypoxia may cause organ dysfunction, but not much is known about tissue oxygenation in the intraoperative setting. We studied microcirculatory tissue oxygen saturation (StO2) to determine representative values for anesthetized patients undergoing urological surgery and to test the hypothesis that StO2 is associated with known perioperative risk factors for morbidity and mortality, conventionally monitored variables, and hypotension requiring norepinephrine. Using near-infrared spectroscopy, we measured StO2 on the thenar eminence in 160 patients undergoing open urological surgery under general anesthesia (FiO2 0.35-0.4), and calculated its correlations with age, risk level for general perioperative complications and mortality (high if age ≥70 and procedure is radical cystectomy), mean arterial pressure (MAP), hemoglobin concentration (Hb), central venous oxygen saturation (ScvO2), and norepinephrine use. The time averaged StO2 was 86 ± 6 % (mean ± SD). In the multivariate analysis, Hb [standardized coefficient (SC) 0.21, p = 0.003], ScvO2 (SC 0.53, p < 0.001) and high risk level (SC 0.06, p = 0.03) were significant independent variables correlated with StO2. SStO2 was partly dependent on MAP only when this was below 65 mmHg (lowest MAP SC 0.20, p = 0.006, MAP area under the curve <65 mmHg SC 0.03, p = 0.02). Finally, StO2 was slightly lower in patients requiring norepinephrine (85 ± 6 vs. 89 ± 6 %, p = 0.001). Intraoperative StO2 in urological patients was comparable to that of healthy volunteers breathing room air as reported in the literature and correlated with known perioperative risk factors. Further research should investigate its association with outcome and the effect of interventions aimed at optimizing StO2.

Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background and current applications.

Conventional cardiovascular monitoring may not detect tissue hypoxia, and conventional cardiovascular support aiming at global hemodynamics may not restore tissue oxygenation. NIRS offers non-invasive online monitoring of tissue oxygenation in a wide range of clinical scenarios. NIRS monitoring is commonly used to measure cerebral oxygenation (rSO(2)), e.g. during cardiac surgery. In this review, we will show that tissue hypoxia occurs frequently in the perioperative setting, particularly in cardiac surgery. Therefore, measuring and obtaining adequate tissue oxygenation may prevent (postoperative) complications and may thus be cost-effective. NIRS monitoring may also be used to detect tissue hypoxia in (prehospital) emergency settings, where it has prognostic significance and enables monitoring of therapeutic interventions, particularly in patients with trauma. However, optimal therapeutic agents and strategies for augmenting tissue oxygenation have yet to be determined.

The differential effects of recombinant brain natriuretic peptide, nitroglycerine and dihydralazine on systemic oxygen delivery and gastric mucosal microvascular oxygenation in dogs.

Brain natriuretic peptide has vasodilatory properties and may thus increase splanchnic perfusion and oxygenation. We compared the effects of recombinant brain natriuretic peptide on gastric mucosal microvascular haemoglobin oxygenation (reflectance spectrophotometry) and systemic variables with those of equi-hypotensive doses of two other vasodilators (nitroglycerine and dihydralazine). Chronically instrumented, healthy dogs were randomly allocated to receive on different days, one of the three drugs (nitroglycerine and dihydralazine doses titrated to reduce mean arterial pressure by ∼20%). Brain natriuretic peptide significantly increased gastric mucosal microvascular haemoglobin oxygenation selectively, i.e. without concomitant haemodynamic effects. In contrast, the other vasodilators either did not increase gastric mucosal microvascular haemoglobin oxygenation at all (nitroglycerine), or did so only with marked increases in other systemic haemodynamic variables (dihydralazine). Our data suggest a potential role of recombinant brain natriuretic peptide selectively for increasing microvascular mucosal oxygenation. Studies are required to extend these findings to the clinical setting.

Paresis of cranial nerve VI (N. abducens) after thoracic dural perforation.

Epidural anesthesia is associated with the risk of unintended dural perforation and concomitant leakage of cerebrospinal fluid (CSF) from the subarachnoidal space. This may remain asymptomatic or trigger post-dural puncture headache (PDPH). Cerebral nerve lesions after attempted epidural anesthesia are very rare. Here we report a case of unilateral paresis of the cranial nerve VI (N. abducens) after attempted thoracic epidural anesthesia. Herein, diagnosis of N. abducens paresis was probably delayed because the optical symptoms, such as blurred and double vision, were attributed to optical hallucinations caused by a concomitant (S)-ketamine infusion. In all patients with optical symptoms such as blurred or double vision a paresis of the abducens nerve should be considered.

Sevoflurane and propofol anaesthesia differentially modulate the effects of epinephrine and norepinephrine on microcirculatory gastric mucosal oxygenation.

BACKGROUND: Adequate gastrointestinal mucosal oxygenation is regarded to be crucial in the prevention and therapy of critical illness. Epinephrine and norepinephrine are used for perioperative haemodynamic support. However, their per se effects on gastromucosal haemoglobin oxygenation (µHbO(2)) remain unclear. Moreover, respective effects of epinephrine and norepinephrine may be affected by the type of underlying anaesthesia. Thus, we studied the effects of epinephrine and norepinephrine during anaesthesia with sevoflurane or propofol on regional gastromucosal µHbO(2) and systemic O(2)-derived variables. METHODS: In a double-randomized cross-over study, chronically instrumented dogs (n=6 per group) were anaesthetized randomly with sevoflurane or propofol, ventilated, and then randomly received either epinephrine or norepinephrine (0, 0.05, 0.1, and 0.2 µg kg(-1) min(-1)). We measured gastromucosal µHbO(2), systemic haemodynamics, and O(2)-derived variables. RESULTS: During sevoflurane anaesthesia, norepinephrine markedly increased µHbO(2) (P<0.0001) and systemic oxygen transport (DO(2)) (P=0.0006). In contrast, epinephrine failed to increase µHbO(2), despite doubling DO(2) (P=0.0002). During propofol anaesthesia, in contrast to sevoflurane, neither epinephrine nor norepinephrine affected µHbO(2), although epinephrine, but not norepinephrine, again resulted in markedly increased DO(2) (P<0.0001). CONCLUSIONS: The effects of epinephrine and norepinephrine depended on the type of anaesthesia. In addition, regional effects (i.e. µHbO(2)) were not predictable from systemic effects (i.e. DO(2)).

Cormack-Lehane classification revisited.

BACKGROUND: The Cormack-Lehane (CL) classification is broadly used to describe laryngeal view during direct laryngoscopy. This classification, however, has been validated by only a few studies reporting inconclusive data concerning its reliability. This discrepancy between widespread use and limited evidence prompted us to investigate the knowledge about the classification among anaesthesiologists and its intra- and inter-observer reliability. METHODS: One hundred and twenty interviews were performed at a major European anaesthesia congress. Participants were interviewed about their general knowledge on grading systems to classify laryngeal view during laryngoscopy and were subsequently asked to define the grades of the CL classification. Inter- and intra-observer reliabilities were tested in 20 anaesthesiologists well familiar with the CL classification, who performed 100 laryngoscopies in a full-scale patient simulator. RESULTS: Although 89% of interviewed subjects claimed to know a classification to describe laryngeal view during laryngoscopy, 53% were able to name a classification. When specifically asked about the CL classification, 74% of the interviewed subjects stated to know this classification, whereas 25% could define all four grades correctly. In the simulator-based part of the study, inter-observer reliability was fair with a kappa coefficient of 0.35 and intra-observer reliability was poor with a kappa of 0.15. CONCLUSIONS: The CL classification is poorly known in detail among anaesthesiologists and reproducibility even in subjects well familiar with this classification is limited.

Preconditioning, but not postconditioning, with Sevoflurane reduces pulmonary neutrophil accumulation after lower body ischaemia/reperfusion injury in rats.

BACKGROUND AND OBJECTIVES: Aortic ischaemia and reperfusion may induce pulmonary sequestration of neutrophil granulocytes. Preconditioning and postconditioning with volatile anaesthetics confer protection against reperfusion injury in various organs, such as heart, kidneys or brain. We tested the hypothesis that pre- or postconditioning with Sevoflurane attenuates pulmonary neutrophil accumulation after ischaemia/reperfusion injury of the aorta. METHODS: Anaesthetized and mechanically ventilated Wistar rats underwent laparotomy and were randomly assigned to one of the following groups: Sham (n = 10), ischaemia/reperfusion (n = 8, lower body ischaemia by clamping of the infrarenal aorta for 2 h followed by 3 h of reperfusion), preconditioning (n = 10, 2.0% Sevoflurane administered over 30 min prior to ischaemia) and postconditioning (n = 9, 2.0% Sevoflurane during reperfusion). Following reperfusion, the lungs were removed for microscopic determination of neutrophil accumulation. RESULTS: Ischaemia/reperfusion induced a significant increase in pulmonary neutrophil accumulation (mean +/- SD, 29.9 +/- 7.4 vs. 15.8 +/- 6.6 neutrophils per microscopic field in ischaemia/reperfusion vs. Sham, respectively, P < 0.001). Sevoflurane preconditioning resulted in a lower neutrophil count (20.3 +/- 7.1 neutrophils, P < 0.001 vs. ischaemia/reperfusion), while postconditioning showed no effects (25.8 +/- 9.8 neutrophils vs. ischaemia/reperfusion, not significant). CONCLUSIONS: Preconditioning, but not postconditioning, with Sevoflurane reduces pulmonary neutrophil accumulation after ischaemia/reperfusion injury of the lower body. Since neutrophil accumulation plays a major role in the pathophysiology of acute lung injury, our data suggest a protective effect of Sevoflurane preconditioning on remote pulmonary ischaemia/reperfusion injury.

The NO donor SIN-1 improves intestinal-arterial P(CO(2)) gap in experimental endotoxemia: an animal study.

BACKGROUND: Dysfunction of the microcirculation is a prominent feature of sepsis and endotoxemia. Recently, it has been shown that microcirculatory alterations are completely reversed by local or systemic application of vasodilators in severely septic patients. Therefore, we investigated the influence of vasodilator therapy on microcirculatory dysfunction of the ileum during endotoxic shock in a prospective, controlled animal study. METHODS: After baseline measurements, shock was induced in 12 domestic pigs by lipopolysaccharide via the mesenteric vein until the mean arterial pressure fell below 60 mmHg. After 30 min in shock, six animals were resuscitated with either fluid alone (control) or fluid and 2 microg/kg/min of the vasodilator 3-morpholino-sydnonimine (SIN-1). The systemic and regional hemodynamics and oxygenation parameters, tonometric ileal P(CO(2)) and microvascular oxygen pressures (muP(O(2))) (by oxygen-dependent Pd-porphyrin phosphorescence) were measured simultaneously. RESULTS: The ileal-arterial P(CO(2)) gap increased during shock and the ileal mucosal and serosal muP(O(2)) decreased concurrently. SIN-1 in addition to fluid resuscitation significantly improved the ileal-arterial P(CO(2)), whereas fluid alone failed to decrease the P(CO(2)) gap. The SIN-1-induced improvement in the P(CO(2)) gap was accompanied by an increase in serosal muP(O(2)) above shock levels. Mucosal muP(O(2)) was resuscitated to baseline levels in both groups. CONCLUSION: The application of the vasodilator SIN-1 in addition to fluid resuscitation improves the ileal-arterial P(CO(2)) gap and mucosal muP(O(2)), together with a moderate increase in serosal muP(O(2)), after endotoxic shock. This finding is consistent with the concept that vasodilators may correct pathologic flow distribution within the intestinal wall.

Endogenous nitric oxide reduces the efficacy of the endothelin system to maintain blood pressure during high epidural anaesthesia in conscious dogs.

BACKGROUND AND OBJECTIVE: During high epidural anaesthesia, endothelin only contributes minimally to blood pressure stabilization. This phenomenon could result from the inhibitory action of nitric oxide on the endothelin system. To clarify this, we studied the interaction between nitric oxide and endothelin during high epidural anaesthesia in conscious dogs, in comparison to the interaction of nitric oxide and vasopressin. METHODS: Six animals were used in 45 individual experiments randomly arranged as follows: N-omega-nitro-arginine-methylester 0.3-10 mg kg-1 under physiological conditions or during high epidural anaesthesia (lidocaine 1%) and N-omega-nitro-arginine-methylester (l-NAME) 0.3-10 mg kg-1 after preceding endothelin (Tezosentan(R)) or vasopressin (beta-mercapto-beta,beta-cyclo-penta-methylene-propionyl-O-Me-Tyr-Arg-vasopressin) receptor blockade under physiological conditions or during high epidural anaesthesia. During control experiments normal saline was injected either intravenously (n = 5) or into the epidural space (n = 4). RESULTS: N-omega-nitro-arginine-methylester increased mean arterial pressure dose-dependently in all groups. However, this effect was substantially reduced in the presence of the endothelin receptor antagonist compared to N-omega-nitro-arginine-methylester alone, both under control conditions (7 +/- 3 vs. 21 +/- 3 mmHg; P < 0.05) and during high epidural anaesthesia (17 +/- 3 vs. 30 +/- 1 mmHg; P < 0.05). Blockade of vasopressin showed no similar relationship with N-omega-nitro-arginine-methylester. CONCLUSIONS: The diminished increase in mean arterial pressure after injection of N-omega-nitro-arginine-methylester only during endothelin receptor blockade indicates that endogenous nitric oxide inhibits the action of endothelin during high epidural anaesthesia and might thus explain the reduced efficacy of endothelin in maintaining blood pressure during high epidural anaesthesia.

Effects of thoracic epidural anaesthesia on microvascular gastric mucosal oxygenation in physiological and compromised circulatory conditions in dogs.

BACKGROUND: The effects of thoracic epidural anaesthesia (TEA) on gastric mucosal microvascular haemoglobin oxygenation (microHbO(2)) are unclear. At the splanchnic level, reduction of sympathetic tone may promote vasodilation and increase microHbO(2). However, these splanchnic effects are counteracted by systemic effects of TEA (e.g., decreased cardiac output (CO) and mean arterial pressure (MAP)), thus making the net effect on microHbO(2) difficult to predict. In this respect, effects of TEA on microHbO(2) may differ between physiological and compromised circulatory conditions, and additionally may depend on adequate fluid resuscitation. Furthermore, TEA may alter the relationship between regional microHbO(2) and systemic oxygen-transport (DO(2)). METHODS: Chronically instrumented dogs (flow probes for CO measurement) were anaesthetized, their lungs ventilated and randomly received TEA with lidocaine (n=6) or epidural saline (controls, n=6). Animals were studied under physiological and compromised circulatory conditions (PEEP 10 cm H(2)O), both with and without fluid resuscitation. We measured gastric mucosal microHbO(2) by reflectance spectrophotometry, systemic DO(2), and systemic haemodynamics (CO, MAP). RESULTS: Under physiological conditions, TEA preserved microHbO(2) (47 (3)% and 49 (5)%, mean (sem)) despite significantly decreasing DO(2) (11.3 (0.8) to 10.0 (0.7) ml kg(-1) min(-1)) and MAP (66 (2) to 59 (3) mm Hg). However, during compromised circulatory conditions, TEA aggravated the reduction in microHbO(2) (to 32 (1)%), DO(2) (to 6.7 (0.8) ml kg(-1) min(-1)) and MAP (to 52 (4) mm Hg), compared with controls. During TEA, fluid resuscitation completely restored these variables. TEA preserved the correlation between microHbO(2) and DO(2), compared with controls. CONCLUSIONS: TEA maintains microHbO(2) under physiological conditions, but aggravates the reduction of microHbO(2) induced by cardiocirculatory depression, thereby preserving the relationship between gastric mucosal and systemic oxygenation.