Cutaneous Microvascular Blood Flow and Reactivity in Hypoxia.

As is known, hypoxia leads to an increase in microcirculatory blood flow of the skin in healthy volunteers. In this pilot study, we investigated microcirculatory blood flow and reactive hyperemia of the skin in healthy subjects in normobaric hypoxia. Furthermore, we examined differences in microcirculation between hypoxic subjects with and without short-term acclimatization, whether or not skin microvasculature can acclimatize. Fourty-six healthy persons were randomly allocated to either short-term acclimatization using intermittent hypoxia for 1 h over 7 days at an FiO2 0.126 (treatment, n = 23) or sham short-term acclimatization for 1 h over 7 days at an FiO2 0.209 (control, n = 23). Measurements were taken in normoxia and at 360 and 720 min during hypoxia (FiO2 0.126). Microcirculatory cutaneous blood flow was assessed with a laser Doppler flowmeter on the forearm. Reactive hyperemia was induced by an ischemic stimulus. Measurements included furthermore hemodynamics, blood gas analyses and blood lactate. Microcirculatory blood flow increased progressively during hypoxia (12.3 ± 7.1-19.0 ± 8.1 perfusion units; p = 0.0002) in all subjects. The magnitude of the reactive hyperemia was diminished during hypoxia (58.2 ± 14.5-40.3 ± 27.4 perfusion units; p = 0.0003). Short-term acclimatization had no effect on microcirculatory blood flow. When testing for a hyperemic response of the skin's microcirculation we found a diminished signal in hypoxia, indicative for a compromised auto-regulative circulatory capacity. Furthermore, hypoxic short-term acclimatization did not affect cutaneous microcirculatory blood flow. Seemingly, circulation of the skin was unable to acclimatize using a week-long short-term acclimatization protocol. A potential limitation of our study may be the 7 days between acclimatization and the experimental test run. However, there is evidence that the hypoxic ventilatory response, an indicator of acclimatization, is increased for 1 week after short-term acclimatization. Then again, 1 week is what one needs to get from home to a location at significant altitude.

The impact of endotoxin on jejunal tissue oxygenation.

OBJECTIVE: We examined the effects of systemic ETX on jejunal mucoal microcirculatory parameters in anesthetized pigs. METHODS: Jejunal mucosal tissue PO2 was measured employing Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Jejunal microcirculatory blood flow was assessed by laser Doppler flowmetry. Microvascular conductance and rhythmical oscillation of the tissue PO2 were calculated. Systemic hemodynamic variables, mesenteric venous and systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were taken at BL and after Escherichia coli LPS administration in 20 minutes intervals for 110 minutes. RESULTS: ETX infusion led to a significant (P<.05) decrease of PO2 muc (from 24±4 to 8±4 mm Hg) and microvascular HbO2 (from 41±13 to 24±12%). Microcirculatory conductivity increased in ETX animals, microvascular blood flow remained unchanged (PU; from 228±45 to 232±58). ETX induced an increase in oscillation frequency of mucosal tissue oxygenation. CONCLUSIONS: Endotoxinemia resulted in a significant depression of mucosal tissue oxygenation despite a constant microcirculatory blood flow. This impairment of tissue oxygenation resulted in an increase in the vasomotion pattern in a futile attempt to counteract the undersupply of oxygen to the jejunal tissue.

Ultrasound-guided regional anesthesia for carotid endarterectomy induces early hemodynamic and stress hormone changes.

OBJECTIVE: Locoregional anesthesia is an effective method for evaluating cerebral function during carotid endarterectomy (CEA). Landmark-guided regional anesthesia (RA) is currently used for CEA and can provoke substantial perioperative hypertension. Ultrasound-guided RA (US-RA) is a new method for performing RA in CEA; however, the effect on sympathetic activity and blood pressure is uncertain. This study assessed early sympathetic activity during CEA in US-RA compared with general anesthesia (GA). METHODS: Patients were prospectively randomized to receive US-RA (n = 32) or GA (n = 28) for CEA. The primary end point was the change in systolic arterial blood pressure after induction of anesthesia (just before starting surgery) comparing US-RA with GA. We also recorded heart rate and analyzed concentrations of plasma blood hormones, including cortisol, metanephrine, and normetanephrine at five different times. Creatinine kinase, troponin I, and N-terminal pro-B-type natriuretic peptide were analyzed to detect potential changes in cardiac biomarkers during the procedure. RESULTS: Systolic arterial blood pressure (mean ± standard deviation) increased significantly in US-RA patients compared with GA patients even before surgery was initiated (180 ± 26 mm Hg vs 109 ± 24 mm Hg; P < .001), then remained elevated during the entire surgery and returned to baseline values 1 hour after admission to the postoperative anesthesia care unit. Heart rate (US-RA: 78 ± 16 beats/min, GA: 52 ± 12 beats/min; P < .001) and cortisol levels (US-RA: 155 ± 97 µg/L, GA: 99 ± 43 µg/L; P = .006) were also significantly higher in the US-RA group after induction of anesthesia. Other values did not differ. CONCLUSIONS: The US-RA technique for CEA induces temporary intraoperative hypertension and an increase in stress hormone levels. Nevertheless, US-RA is a feasible, effective, and safe form of locoregional for CEA that enables targeted placement of low volumes of local anesthesia under direct visualization.

A prediction model for out-of-hospital cardiopulmonary resuscitation.

BACKGROUND: We created a prediction model to be used in cardiopulmonary resuscitation (CPR) attempts as a decision tool to omit futile CPR attempts and to save resources. METHODS: In this post hoc analysis, we assessed predictive parameters for neurological recovery after successful CPR. The original study was designed as a blinded, randomized, prospective, controlled, multicenter clinical trial. RESULTS: We identified 1166 prehospital cardiac arrest patients being treated with advanced cardiac life support. Seven hundred eighty-six of 1166 patients (67.4%) died at the scene and 380 of 1166 (32.6%) were brought to the hospital. Two hundred sixty-five of 1166 patients (22.7%) died in the hospital. One hundred fifteen of 1166 (9.8%) were discharged from the hospital and 92 of the 115 patients (80%) could be followed-up. Good cerebral performance was regained by 54% of discharged patients (50 of 92 patients). In 46% of patients (42/92), unconsciousness or severe disability remained. Ventricular fibrillation was more likely to have occurred in patients with good neurological recovery (42/50 = 84.0%), whereas asystole was more likely in patients with poor neurological recovery (9/42 = 21.4%). A score was developed to predict the probability of death using logistic regression analysis. Predicting death in the hospital revealed a sensitivity of 99.8% (953/955), but only a specificity of 2.9% (3/104; threshold 0.5). Predicting survival until discharge from the hospital revealed a sensitivity of 99% (103/104), but only a specificity of 8% (72/955; threshold 0.99). A receiver operating characteristic curve yielded an area under the curve of 0.795 (0.751-0.839) at a confidence interval of 95%. CONCLUSION: For out-of-hospital patients with cardiac arrest, parameters documented in the field did not allow accurate prediction of hospital survival.

Gum elastic bougie-guided insertion of the ProSeal laryngeal mask airway is superior to the digital and introducer tool techniques in patients with simulated difficult laryngoscopy using a rigid neck collar.

BACKGROUND: We compared three techniques for insertion of the laryngeal mask airway ProSeal (PLMA) in patients with simulated difficult laryngoscopy using a rigid neck collar. METHODS: Ninety-nine anesthetized healthy female patients aged 19-68 yr were randomly allocated for PLMA insertion using the digital, introducer tool (IT) or guided techniques. Difficult laryngoscopy was simulated using a rigid neck collar. The laryngoscopic view was graded before PLMA insertion. The digital and IT techniques were performed according to the manufacturer's instructions. The guided technique involved priming the drain tube with an Eschmann tracheal tube introducer, placing the introducer in the esophagus under direct vision and railroading the PLMA into position. Failed insertion was defined by any of the following criteria: 1) failed pharyngeal placement, 2) malposition, and 3) ineffective ventilation. RESULTS: The median laryngoscopic view was 3 and the mean interincisor distance was 3.3 cm. Insertion was more frequently successful with the guided technique at the first attempt (guided 100%, digital 64%, IT 61%; P<0.0001), but success after three attempts was similar (guided 100%, digital 94%, IT 91%). The time taken for successful placement was similar among groups at the first attempt, but was shorter for the guided technique after three attempts (guided 31+/-8 s, digital 49+/-28 s, IT 54+/-37 s; P<0.02). CONCLUSION: The guided insertion technique is more frequently successful than the digital or IT techniques in patients with simulated difficult laryngoscopy using a rigid neck collar.

Regional and local brain oxygenation during hemorrhagic shock: a prospective experimental study on the effects of small-volume resuscitation with norepinephrine.

BACKGROUND: Patients with uncontrolled hemorrhage may benefit if resuscitation with large amounts of fluids is replaced by a small volume or vasopressor until surgery. Norepinephrine (NE) is commonly used as a vasopressor to control hypotension. The purpose of this study was to compare the effects of hypertonic-hyperoncotic saline starch solution (HHS) either alone or combined with NE on brain tissue oxygen pressure (PbtO2) and brain oxygen saturation (rSO2) in a model of uncontrolled hemorrhage. METHODS: After approval of the animal investigation committee, 22 anesthetized pigs underwent simulated penetrating liver trauma. At hemodynamic decompensation, animals were randomly assigned to receive HHS (Hyperhaes; 4 mL/kg; n = 8) with normal saline placebo, low-dose NE (low NE; 500 microg, and 1 microg/kg/min; n = 7), or high-dose NE (high NE; 1,000 microg, and 1 microg/kg/min; n = 7). Bleeding was controlled manually 30 minutes after drug administration. RESULTS: Cerebral perfusion pressure (CePP), PbtO2, and rSO2 decreased with hemorrhage in all groups (baseline vs. decompensation, CePP-HHS, 83 +/- 5 mm Hg vs. 9 +/- 1 mm Hg; low NE, 67 +/- 6 mm Hg vs. 16 +/- 2 mm Hg; high NE, 77 +/- 7 mm Hg vs. 15 +/- 1 mm Hg. PbtO2-HHS, 100% vs. 29%; low NE, 100% vs. 33%; high NE, 100% vs. 27%. rSO2-HHS, 100% vs. 70%; low NE, 100% vs. 76%; high NE, 100% vs. 63%). Therapy with HHS, low NE, and high NE resulted in a comparable increase of CePP, PbtO2, and rSO2, respectively (5 minutes after therapy, CePP-HHS, 29 +/- 3 mm Hg; low NE, 27 +/- 3 mm Hg; high NE, 28 +/- 3 mm Hg. PbtO2-HHS, 207%; low NE, 129%; high NE, 170%. rSO2-HHS, 94%; low NE, 83%; high NE, 87%). Overall survival was six of eight, four of seven, and six of seven, respectively. CONCLUSION: After uncontrolled hemorrhagic shock, addition of different dosages of NE to HHS, compared with HHS alone, showed no beneficial effect on CePP, rSO2, or PbtO2.

Release of protein S100B in haemorrhagic shock: effects of small volume resuscitation combined with arginine vasopressin.

BACKGROUND: The present study was designed to evaluate the effect of conventional fluid resuscitation and small volume resuscitation alone and combined with arginine vasopressin (AVP) on cerebral perfusion pressure (CPP) and protein S100B during experimental haemorrhagic shock. MATERIAL AND METHODS: Thirty anaesthetised pigs underwent a penetrating liver trauma. Following haemodynamic decompensation, pigs received either (1) a combination of crystalloid (40 mL kg(-1)) and colloid (20 mL kg(-1)) solutions (fluid, n=10), (2) hypertonic-hyperoncotic solution (HHS; 4 mL kg(-1)) combined with normal saline (HHS+NS; n=10) or (3) HHS combined with AVP (0.2 U kg(-1) followed by an infusion of 2 U kg(-1)h(-1); HHS+AVP; n=10). RESULTS: Compared to baseline, CPP decreased and S100B levels increased significantly at haemodynamic decompensation (S100B: fluid, 0.52+/-0.23 microg L(-1) vs. 0.85+/-0.37 microg L(-1), p<0.05; HHS+NS, 0.47+/-0.18 microg L(-1) vs. 0.90+/-0.33 microg L(-1), p<0.05; HHS+AVP, 0.53+/-0.18 microg L(-1) vs. 0.90+/-0.39 microg L(-1), p<0.01). During the initial 10 min of therapy, CPP of HHS+NS was significantly higher compared to the fluid group, increased more rapidly in the HHS+AVP group, but was not significantly different thereafter. S100B levels decreased close to baseline values (p<0.001), and did not differ between groups. CONCLUSION: HHS+AVP resulted in higher CPP compared to fluid and HHS+NS in the initial phase of therapy, but did not differ thereafter. Haemorrhage-induced hypotension yielded increased S100B levels that were comparable in groups throughout the study period.

Endogenous vasopressin and copeptin response in multiple trauma patients.

Endogenous arginine vasopressin (AVP) levels in multiple trauma patients are unknown. Arginine vasopressin is considered to play an important role in severe hemorrhage. In this prospective study, 87 multiple trauma patients (Injury Severity Score >15) and 50 healthy volunteers were enrolled. On admission to the emergency department (ED), demographic, clinical, and laboratory data were documented, and blood was sampled for determination of AVP (radioimmunosassay) and copeptin, a stable fragment of the AVP precursor (immunoluminometric assay). In patients requiring intensive care unit (ICU) therapy, blood and data sampling were repeated at 4, 6, and 24 h after ED admission. Linear logistic and mixed-effects regression analyses were used for statistical analysis. On ED admission, AVP plasma concentrations (43.2 +/- 84.9 pM) were significantly increased when compared with controls (0.92 +/- 0.44 pM, P < 0.001). Plethysmographic oxygen saturation was the only parameter independently associated with AVP (regression coefficient, -0.126; 95% confidence interval, -0.237 to -0.014; P = 0.03). No correlation was observed between AVP and survival (P = 0.62), hemodynamic variables (systolic arterial pressure, P = 0.24; MAP, P = 0.59; diastolic arterial pressure, P = 0.74; central venous pressure, P = 0.36), or brain trauma (P = 0.46). In ICU patients, AVP decreased during the first 24 h (P < 0.001) and was independently associated with heart rate (P = 0.02) and blood glucose (P = 0.009). Copeptin concentrations were correlated with AVP (r2 = 0.718, P < 0.001). In conclusion, AVP was significantly increased in multiple trauma patients and seems to be an integral part of the neuroendocrine response to severe injury. In ICU patients, AVP decreased to moderately elevated levels within 24 h after ED admission.

A pelvic fracture model for the assessment of treatment options in a laboratory environment.

BACKGROUND: Optimal prehospital and clinical management of patients with severe pelvic trauma is controversial. Prospective evaluations of different treatment strategies have not been performed and treatment is currently not evidence-based. The purpose of the present study was to develop a porcine model of reproducible severe pelvic trauma for subsequent laboratory trials. METHODS: The study was performed on 13 juvenile porcine cadavers. Pelvic fractures were created by applying a pure anterior-posterior compression load to the pelvic ring using a servohydraulic material testing machine. Fracture patterns were classified according to the Young-Burgess classification and the Tile classification using postfracture CT scans including 3D-reconstructions. RESULTS: Disruptions of the posterior pelvic ring segment were unilateral in 12 cases and bilateral in one case transforaminal vertical sacrum fractures. Injuries of the anterior ring segment were obturator ring fractures bilateral, ipsilateral or contralateral to the injury of the posterior ring segment. According to the Tile classification this resulted in 12 type C1 and 1 type C3 fractures. In the Young classification all injuries were classified as type APC III. In six cases transverse process fractures were found ipsilateral to the posterior ring disruption. Initial force drops indicating bony or ligamentous injuries occurred at mean forces of 4030 +/- 269N (range, 3617-4374N). CONCLUSION: The present model was able to create reproducible unstable pelvic fractures and can be used for controlled laboratory trials to study the management of patients with pelvic fractures.

Brain tissue oxygen pressure and cerebral metabolism in an animal model of cardiac arrest and cardiopulmonary resuscitation.

OBJECTIVE: Direct measurement of brain tissue oxygenation (PbtO2) is established during spontaneous circulation, but values of PbtO2 during and after cardiopulmonary resuscitation (CPR) are unknown. The purpose of this study was to investigate: (1) the time-course of PbtO2 in an established model of CPR, and (2) the changes of cerebral venous lactate and S-100B. METHODS: In 12 pigs (12-16 weeks, 35-45 kg), ventricular fibrillation (VF) was induced electrically during general anaesthesia. After 4 min of untreated VF, all animals were subjected to CPR (chest compression rate 100/min, FiO2 1.0) with vasopressor therapy after 7, 12, and 17 min (vasopressin 0.4, 0.4, and 0.8 U/kg, respectively). Defibrillation was performed after 22 min of cardiac arrest. After return of spontaneous circulation (ROSC), the pigs were observed for 1h. RESULTS: After initiation of VF, PbtO2 decreased compared to baseline (mean +/- SEM; 22 +/- 6 versus 2 +/- 1 mmHg after 4 min of VF; P < 0.05). During CPR, PbtO2 increased, and reached maximum values 8 min after start of CPR (25 +/- 7 mmHg; P < 0.05 versus no-flow). No further changes were seen until ROSC. Lactate, and S-100B increased during CPR compared to baseline (16 +/- 2 versus 85 +/- 8 mg/dl, and 0.46 +/- 0.05 versus 2.12 +/- 0.40 microg/l after 13 min of CPR, respectively; P < 0.001); lactate remained elevated, while S-100B returned to baseline after ROSC. CONCLUSIONS: Though PbtO2 returned to pre-arrest values during CPR, PbtO2 and cerebral lactate were lower than during post-arrest reperfusion with 100% oxygen, which reflected the cerebral low-flow state during CPR. The transient increase of S-100B may indicate a disturbance of the blood-brain-barrier.

Cutaneous vascular reactivity and flow motion response to vasopressin in advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome.

INTRODUCTION: Disturbances in microcirculatory homeostasis have been hypothesized to play a key role in the pathophysiology of multiple organ dysfunction syndrome and vasopressor-associated ischemic skin lesions. The effects of a supplementary arginine vasopressin (AVP) infusion on microcirculation in vasodilatory shock and postoperative multiple organ dysfunction syndrome are unknown. METHOD: Included in the study were 18 patients who had undergone cardiac or major surgery and had a mean arterial blood pressure below 65 mmHg, despite infusion of more than 0.5 microg/kg per min norepinephrine. Patients were randomly assigned to receive a combined infusion of AVP/norepinephrine or norepinephrine alone. Demographic and clinical data were recorded at study entry and after 1 hour. A laser Doppler flowmeter was used to measure the cutaneous microcirculatory response at randomization and after 1 hour. Reactive hyperaemia and oscillatory changes in the Doppler signal were measured during the 3 minutes before and after a 5-minute period of forearm ischaemia. RESULTS: Patients receiving AVP/norepinephrine had a significantly higher mean arterial pressure (P = 0.047) and higher milrinone requirements (P = 0.025) than did the patients who received norepinephrine only at baseline. Mean arterial blood pressure significantly increased (P < 0.001) and norepinephrine requirements significantly decreased (P < 0.001) in the AVP/norepinephrine group. Patients in the AVP/norepinephrine group exhibited a significantly higher oscillation frequency of the Doppler signal before ischaemia and during reperfusion at randomization. During the study period, there were no differences in either cutaneous reactive hyperaemia or the oscillatory pattern of vascular tone between groups. CONCLUSION: Supplementary AVP infusion in patients with advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome did not compromise cutaneous reactive hyperaemia and flowmotion when compared with norepinephrine infusion alone.

Value of transducer positions in the measurement of finger flexor tendon thickness by sonography.

OBJECTIVE: To assess the value of 2 transducer positions for measurement of finger flexor tendon thickness by sonography. METHODS: Flexor tendon thickness of the third finger was measured sonographically by 2 independent investigators in 20 healthy volunteers (n = 40 fingers) and in 4 cadaveric specimens (n = 4 fingers). Flexor tendon thickness was measured at histologic examination in the cadaveric specimens. We defined the area of the A1 annular pulley as position I and the area of the A2 annular pulley as position II. Sonographic measurements were performed in transverse (dorsovolar and radioulnar) and longitudinal planes. Interobserver and intraobserver variabilities were evaluated by each investigator performing 3 measurements at each position. RESULTS: In position I, volunteers had flexor tendon thickness of 2.7 to 4.0 mm (mean +/- SD, 3.28 +/- 0.26 mm) longitudinally; transversally the thickness was 2.5 to 4.0 mm (mean, 3.34 +/- 0.29 mm) dorsovolar and 5.5 to 8.9 mm (mean, 7.34 +/- 0.71) radioulnar in position I. Position II revealed thickness of 3.2 to 4.2 mm (mean, 3.6 +/- 0.23 mm) longitudinally; transversally the thickness was 2.7 to 4.1 mm (mean, 3.4 +/- 0.27) dorsovolar and 4.3 to 6.8 mm (mean, 5.27 +/- 0.65) radioulnar. Interobserver and intraobserver variability for position I was better than for position II (P < .01 versus P < .05). Sonographic findings correlated excellently with histologic findings (r2 = 0.94). CONCLUSIONS: Standardized transducer positions for sonographic measurements of finger flexor tendon thickness showed good interobserver and intraobserver variability. Position I was found to be more reliable than position II.

Effects of vasopressin on adrenal gland regional perfusion during experimental cardiopulmonary resuscitation.

OBJECTIVE: Despite the important role of the adrenal gland during cardiac arrest, little is known about changes in the adrenal medullary or cortical blood flow in this setting. This study was designed to assess regional adrenal gland perfusion in the medulla and cortex during cardiopulmonary resuscitation (CPR), and after administration of adrenaline (epinephrine) versus vasopressin versus saline placebo. METHODS: After 4 min of untreated ventricular fibrillation, and 3 min of basic life support CPR, 19 animals were randomly assigned to receive either vasopressin (0.4 U/kg; n=7), adrenaline (45 microg/kg; n=6) or saline placebo (n=6), respectively. Haemodynamic variables, adrenal, and renal blood flow were measured after 90 s of CPR, and 90 s and 5 min after drug administration. RESULTS: All values are given as mean+/-S.E.M. Blood flow in the adrenal medulla was significantly higher 90 s after adrenaline when compared with saline placebo in the right adrenal medulla (210+/-14 vs. 102+/-5 ml/min per 100 mg), and in the left adrenal medulla (218+/-14 vs. 96+/-3 ml/min per 100 mg). Blood flow in the adrenal medulla was significantly higher 90 s and 5 min after vasopressin when compared with adrenaline in the right (326+/-22 mg vs. 210+/-14 ml/min per 100 mg, and 297+/-17 vs. 103+/-5 ml/min per 100 mg), and in the left medulla (333+/-25 vs. 218+/-14 ml/min per 100 mg, and 295+/-14 vs. 111+/-7 ml/min per 100 mg). Ninety seconds and five minutes after vasopressin, and 90 s after adrenaline, adrenal cortex blood flow was significantly higher when compared with saline placebo. After 12 min of cardiac arrest, including 8 min of CPR, seven of seven pigs in the vasopressin group, one of six pigs in the adrenaline group, but none of six placebo were successfully defibrillated. CONCLUSION: Both vasopressin and adrenaline produced significantly higher medullary and cortical adrenal gland perfusion during CPR than did a saline placebo; but vasopressin resulted in significantly higher medullary adrenal gland blood flow when compared with adrenaline.