Assessment of autonomic function after acute spinal cord injury using heart rate variability analyses.

OBJECTIVES: Spinal cord injury (SCI) often results in severe dysfunction of the autonomic nervous system. C1-C8 SCI affects the supraspinal control to the heart, T1-T5 SCI affects the spinal sympathetic outflow to the heart, and T6-T12 SCI leaves sympathetic control to the heart intact. Heart rate variability (HRV) analysis can serve as a surrogate measure of autonomic regulation. The aim of this study was to investigate changes in HRV patterns and alterations in patients with acute traumatic SCI. METHODS: As soon as possible after SCI patients who met the inclusion criteria had 24 h Holter monitoring of their cardiac rhythm, additional Holter monitoring were performed 1, 2, 3 and 4 weeks after SCI. RESULTS: Fifty SCI patients were included. A significant increase in standard deviation of the average normal-to-normal (SDANN) sinus intervals was seen in the first month after injury (P=0.008). The increase was only significant in C1-T5 incomplete patients and in patients who did not experience one or more episodes of cardiac arrest. Significant lower values of Low Frequency Power, Total Power and the Low Frequency over High Frequency ratio were seen in the C1-T5 SCI patients compared with T6-T12 SCI patients. CONCLUSIONS: The rise in SDANN in the incomplete C1-T5 patients could be due to spontaneous functional recovery caused by synaptic plasticity or remodelling of damaged axons. That the autonomic nervous system function differs between C1-C8, T1-T5 and T6-T12 patients suggest that the sympathovagal balance in both the C1-C8 and T1-T5 SCI patients has yet to be reached.

Update on acute endovascular and surgical stroke treatment.

Emergency stroke care has become a natural part of the emerging discipline of neurocritical care and demands close cooperation between the neurologist and neurointerventionists, neurosurgeons, and anesthesiologists. Endovascular treatment (EVT), including intra-arterial thrombolysis, mechanical thrombectomy and angioplasty/stenting, is under rapid development. Although EVT has yet to be shown in randomized controlled trials to improve clinical outcome compared to intravenous thrombolysis, it is far better in achieving recanalization of occluded large cerebral vessels, which is crucial for rescuing the penumbra. Moreover, decompressive craniectomy is now a well-established treatment option for malignant middle cerebral artery infarction and cerebellar stroke. Using a case-based approach, this article reviews recent achievements in advanced treatment options for patients with acute ischemic stroke.

High sCD40L levels early after trauma are associated with enhanced shock, sympathoadrenal activation, tissue and endothelial damage, coagulopathy and mortality.

BACKGROUND: Severe injury activates the sympathoadrenal, hemostatic and inflammatory systems, but a maladapted response may contribute to a poor outcome. Soluble CD40L is a platelet-derived mediator that links inflammation, hemostasis and vascular dysfunction. OBJECTIVES: To investigate the association between the sCD40L level and tissue injury, shock, coagulopathy and mortality in trauma patients. METHODS: A prospective, observational study of 80 trauma patients admitted to a Level I Trauma Center. Data on demography, biochemistry, Injury Severity Score (ISS) and 30-day mortality were recorded and admission plasma/serum analyzed for sCD40L and biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments [hcDNA], Annexin V, thrombomodulin and syndecan-1), coagulation activation/inhibition (PF1.2, TAT-complex, antithrombin, protein C, activated protein C, sEPCR, TFPI, von Willebrand factor [VWF], fibrinogen and factor [F] XIII), fibrinolysis (D-dimer, tissue plasminogen activator [tPA] and plasminogen activator inhibitor-1 [PAI-1]) and inflammation (interleukin-6 [IL-6] and sC5b-9). We compared patients stratified by median sCD40L level and investigated predictive values of sCD40L for mortality. RESULTS: High circulating sCD40L was associated with enhanced tissue and endothelial damage (ISS, hcDNA, Annexin V, syndecan-1 and sTM), shock (pH, standard base excess), sympathoadrenal activation (adrenaline) and coagulopathy evidenced by reduced thrombin generation (PF1.2), hyperfibrinolysis (D-dimer), increased activated partial thromboplastin time (APTT) and inflammation (IL-6) (all P < 0.05). A higher ISS (P = 0.017), adrenaline (P = 0.049) and platelet count (P = 0.012) and lower pH (P =0.002) were associated with higher sCD40L by multivariate linear regression analysis. High circulating sCD40L (odds ratio [OR] 1.84 [95% CI 1.05-3.23], P = 0.034), high age (P = 0.002) and low Glasgow Coma Score (GCS) pre-hospital (P = 0.002) were independent predictors of increased mortality. CONCLUSIONS: High early sCD40L levels in trauma patients reflect tissue injury, shock, coagulopathy and sympathoadrenal activation and predict mortality. As sCD40L has pro-inflammatory activity and activates the endothelium, sCD40L may be involved in trauma-induced endothelial damage and coagulopathy.

Alteplase (rtPA) treatment of intraventricular hematoma (IVH): safety of an efficient methodological approach for rapid clot removal.

Intraventricular hemorrhage (IVH) subsequent to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) is associated with high mortality and morbidity. The use of fibrinolytic agents to treat this condition has previously been reported in small clinical trials with limited numbers of patients. Variability regarding inclusion criteria, method of administration and outcome have made it difficult to draw firm conclusions regarding the efficacy of antifibrinolytic therapy. Nine patients with CT-diagnosed IVH were treated with Alteplase intrathecally for 3 to 5 days according to the CT-verified clearance of IVH. After the treatment period, a repeat CT scan was performed to evaluate treatment effect.In this safety study, we achieved rapid removal of IVH compared to retrospective controls, without incidents of re-bleeding, with only 33% permanent shunt placements and a neurological outcome of GOS of 4-5 in 44% of the patients. Based on the above results, the treatment protocol was considered safe and highly effective. A prospective randomized national multicenter trial has been initiated in order to evaluate the efficacy of this novel method also in terms of outcome and shunt dependency.

Endogenous NO does not regulate baseline pulmonary pressure, but reduces acute pulmonary hypertension in dogs.

UNLABELLED: It has remained unclear whether endogenous production of nitric oxide (NO) plays an important role in the regulation of physiologically normal pulmonary pressures. Severe alveolar hypoxia is accompanied by decreased pulmonary NO production, which could contribute to the development of hypoxic pulmonary hypertension. On the other hand, pharmacological NO inhibition further augments this hypertensive response. AIMS: The aims of the present study were to test: (a) whether NO contributes importantly in the maintenance of baseline pulmonary pressure; and (b) to which degree NO is involved in the pulmonary haemodynamic adjustments to alveolar hypoxia. METHODS: In anaesthetized dogs (n=37), the systemic and pulmonary haemodynamic effects of the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 20 mg kg(-1)) and substrate, L-arginine (200-500 mg kg(-1)), were determined at baseline and during alveolar hypoxia. Constant blood flows were accomplished by biventricular bypass, and systemic normoxaemia was maintained by extracorporeal oxygenation. RESULTS: The primary findings were: (a) L-NAME failed to increase baseline mean pulmonary arterial pressure (10.1 +/- 0.7 vs. 10.5 +/- 0.5 mmHg, P=ns), despite effective NO synthase inhibition as evidenced by robust increases in systemic arterial pressures; (b) L-NAME augmented the pulmonary hypertensive response to alveolar hypoxia (10.2 +/- 0.7 to 19.5 +/- 1.7 with L-NAME vs. 9.9 +/- 1.1 to 15.5 +/- 1.0 mmHg without L-NAME, P<0.05); and (c) L-arginine failed to decrease baseline or elevated pulmonary pressures. Instead, prolonged L-arginine caused increases in pulmonary pressure. CONCLUSION: These findings suggest that NO plays no significant role in the tonic physiological control of pulmonary pressure, but endogenous NO becomes an important vasodilatory modulator during elevated pulmonary pressure.

Effect of alveolar hypoxia on segmental pulmonary vascular resistance and lung fluid balance in dogs.

In a biventricular bypass preparation with constant-flow perfusion, pulmonary arterial pressure (Ppa), average pulmonary capillary pressure (Ppc), venous pressure (Pv), extravascular lung water volume (EVWd) and capillary permeability-surface area product for urea (PS) were determined in control animals and in animals subjected to alveolar hypoxia. During hypoxia, Ppa increased in a biphasic manner, the site of hypoxic pulmonary vasoconstriction being located in the arterial upstream segment. At baseline, Ppc values were identical in control and experimental animals (3.4 +/- 0.4 vs. 3.6 +/- 0.2 mmHg). During 150 min of airway hypoxia, the rise in Ppc (5.1 +/- 0.3 mmHg) did not exceed the rise in Ppc (4.9 +/- 0.5 mmHg) recorded in control animals at same time interval during normoxic ventilation. EVWd increased during hypoxia to values significantly higher than those obtained in control animals (0.559 +/- 0.036 vs. 0.466 +/- 0.027 mL water g-1 lung). PS remained unchanged at baseline level throughout experiments in both groups of animals. Present data suggest that lung oedema formation during alveolar hypoxia may be caused by increased transcapillary fluid loss preferentially through transcellular hydraulic pathways in capillary endothelial cells.

[Acute respiratory distress syndrome. Pathogenesis and therapy of acute pulmonary failure]. / Akut respiratorisk distress-syndrom. Patogenese og terapi af akut lungesvigt.

Adult respiratory distress syndrome (ARDS) is the pulmonary response to systemic inflammation precipitated by local or systemic tissue hypoxia, or ischaemia and reperfusion. ARDS is a dynamic, pathological process with a multifactorial etiology. The main clinical manifestations of ARDS are dyspnoea, non-cardiogenic pulmonary oedema, and hypoxia due to increased pulmonary capillary permeability, pulmonary vasoconstriction and diminished pulmonary vascular reactivity. Eventually this pulmonary pathology results in first, oedema, pulmonary hypertension, and increased ventilation-perfusion inequality and later, pulmonary remodelling and irreversible pulmonary hypertension. The inflammatory mechanisms involved in acute lung injury are complex and include activation of polymorphonuclear neutrophils, endothelial cells, and synthesis of free radicals, predominantly derived from oxygen. Cytokines synthesized by macrophages maintain and regulate the inflammatory host response. Immune-modulating therapy in ARDS is yet experimental. Accordingly, treatment in ARDS is supportive, directed towards pulmonary oedema, pulmonary hypertension and hypoxaemia. The use of low tidal volumes and low inspiratory pressures in mechanical ventilation is established therapy. The goal in haemodynamic monitoring by applying a Swan-Ganz catheter is to obtain a low pulmonary capillary wedge pressure (< 12-15 mmHg) without compromising adequate delivery of oxygen to vital organs. For treatment of pulmonary hypertension nitric oxide is useful. Change of position and inhalation with beta2-agonists are therapeutic possibilities. Steroids may be of benefit in the late proliferative phase of ARDS.

Effect of prolonged alveolar hypoxia on pulmonary arterial pressure and segmental vascular resistance.

The time course of hypoxic pulmonary vasoconstriction and its segmental distribution were studied during prolonged (150 min) alveolar hypoxia in in vivo dog lungs at constant-flow perfusion. With the pulmonary and the systemic circulations separated by two extracorporeal circuits, adequate systemic oxygenation was achieved throughout the experiments. The pulmonary circulation exhibited a time-related biphasic hypoxic vasoconstrictor response: an initial rapid contraction [79 +/- 11% (SE) above control level] was followed by a partial relaxation when a second slow and sustained vasoconstriction (92 +/- 13% above control level) superseded. We partitioned the pulmonary circulation into two segments by arterial occlusion: an upstream arterial segment and a downstream segment consisting of a middle and a venous segment. Measurements were performed at baseline and during the late sustained vasoconstrictor response. Prolonged alveolar hypoxia increased pulmonary capillary pressure by 90 +/- 18%, the site of pulmonary vasomotion being the arterial upstream and downstream middle and venous segments.