Silvana Naredi

Increased Sympathetic Nervous Activity in Patients With Nontraumatic Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE Activation of the sympathetic nervous system, which leads to elevation of circulating catecholamines, is implicated in the genesis of cerebral vasospasm and cardiac aberrations after subarachnoid hemorrhage. To this juncture, sympathetic nervous testing has relied on indirect methods only. METHODS We used an isotope dilution technique to estimate the magnitude and time course of sympathoadrenal activation in 18 subarachnoid patients. RESULTS Compared with 2 different control groups, the patients with subarachnoid hemorrhage exhibited an approximately 3-fold increase in total-body norepinephrine spillover into plasma within 48 hours after insult (3.2+/-0.3 and 4.2+/-0.7 versus 10.2+/-1.4 nmol/L; P<0.05 versus both). This sympathetic activation persisted throughout the 7- to 10-day examination period and was normalized at the 6-month follow-up visit. CONCLUSIONS The present study has established that massive sympathetic nervous activation occurs in patients after subarachnoid hemorrhage. This overactivation may relate to the well-known cardiac complications described in subarachnoid hemorrhage.

An outcome study of severe traumatic head injury using the "Lund therapy" with low-dose prostacyclin

Background: There are two independent head injury outcome studies using the “Lund concept”, and both showed a mortality rate of about 10%, and a favourable outcome (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at controlling intracranial pressure, and improving microcirculation around contusions. Intracranial pressure is controlled by maintaining a normal colloid osmotic pressure and reducing the hydrostatic capillary pressure. Microcirculation is improved by ensuring strict normovolaemia and reducing sympathetic discharge. The endogenous substance prostacyclin with its antiaggregatory/antiadhesive effects may further improve microcirculation, which finds support from a microdialysis‐based clinical study and an experimental brain trauma study. The present clinical outcome study aims at evaluating whether the previously obtained good outcome with the Lund therapy can be reproduced, and whether the addition of prostacyclin has any adverse side‐effects.

The Swedish Malignant Middle cerebral artery Infarction Study: Long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care

Objectives –  Hemicraniectomy in patients with malignant middle cerebral artery (mMCA) infarct may be life‐saving. The long‐term prognosis is unknown.

S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy

Objective: To prospectively study S-100B and neuron specific enolase (NSE) levels in subjects treated for severe head injury (sTBI), and investigate the prognostic value of these biomarkers. Methods: Subjects included in a prospective double blind randomised study for sTBI. Inclusion criteria: Glasgow Coma Score (GCS) ⩽8, age 15–70 years, first recorded cerebral perfusion pressure of >10 mm Hg and arrival <24 h after trauma. Subjects were treated with an intracranial pressure (ICP) targeted therapy. Blood samples for S-100B and NSE were drawn immediately after arrival and every 12 h for 5 days. Outcome was evaluated as Glasgow Outcome Scale (GOS) by independent staff at 3 and 12 months. Results: 48 subjects, mean age 35.5 years, and median GCS 6 were included. The first blood sample was drawn at 15.6 (1.4) h after injury. Initial concentration of S-100B was 1.04 (0.21) μg/l and for NSE 18.94 (2.32) μg/l. The biomarkers were significantly higher in subjects with GCS 3 and in those who died compared with those with GCS 4–8 and GOS 2–5, respectively. Receiver operated characteristic curve analyses of the initial S-100B and NSE levels to GOS dichotomised as unfavourable (GOS 1–3) and favourable (GOS 4–5) showed a weak correlation: AUC 0.585 and 0.555, respectively. Using the dichotomisation dead (GOS 1)/alive (GOS 2–5), the AUC values were 0.687 and 0.734, respectively. Furthermore, a correlation was found between the biomarkers themselves and the biomarkers and ICP. Conclusion: At 3 and 12 months after trauma, no differences in prognostic values between the markers were apparent nor was there any clinical significant value of the markers as predictors of clinical outcome.

Fluid therapy and the use of albumin in the treatment of severe traumatic brain injury

Background: Evidence‐based guidelines for severe traumatic brain injury (TBI) do not include strategies for fluid administration. The protocol used in this study includes albumin administration to maintain normal colloid osmotic pressure and advocates a neutral to slightly negative fluid balance. The aim of this study was to analyze the occurrence of organ failure and the mortality in patients with severe TBI treated by a protocol that includes defined strategies for fluid therapy.

Monoamine metabolism and sympathetic nervous activation following subarachnoid haemorrhage: Influence of gender and hydrocephalus

Subarachnoid haemorrhage is a serious condition, often accompanied by cerebral vasospasm and hydrocephalus, which may result in delayed cerebral ischaemia and neurological deterioration. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system, leading to elevated levels of circulating catecholamines is, at least in part, implicated. In this study, we sought to examine the importance of sympathetic nervous activation and its relation to brain monoaminergic neurotransmission in 25 patients following subarachnoid haemorrhage by examining plasma and cerebrospinal fluid levels of the catecholamines noradrenaline, adrenaline and dopamine, and their metabolites. Total body sympathetic activity was concurrently assessed using isotope dilution methodology. In the early phase following subarachnoid haemorrhage patients exhibited markedly elevated rates of spillover of noradrenaline to plasma (9.11 +/- 1.12 vs. 3.39 +/- 0.26 nmol/min, p < 0.01), with rates being higher in those patients in whom hydrocephalus developed (11.15 +/- 1.40 vs. 7.90 +/- 1.41 nmol/min, p = 0.05). The degree of sympathetic nervous activation tended to be higher in females compared with males. Lower cerebral perfusion pressures were observed in those patients in whom cerebrospinal fluid concentrations of noradrenaline and dopamine metabolites were high. A marked sympathetic nervous activation, more pronounced in women and in those with hydrocephalus, occurs following subarachnoid haemorrhage. The diminished cerebral perfusion seen following subarachnoid bleeding may occur as a result of activation of central catecholaminergic neurones.

Sympathetic nervous activation following subarachnoid hemorrhage: Influence of intravenous clonidine

Background: Subarachnoid hemorrhage is often accompanied by systemic complications and cerebral vasospasm. Elevated levels of circulating catecholamines may be involved in the pathophysiology behind these events. The alpha‐2‐agonist clonidine inhibits sympathetic outflow by a central mechanism. Unrestricted sympathoexcitation may be detrimental and administration of clonidine may be beneficial in these patients.

Absence of electroencephalographic seizure activity in patients treated for head injury with an intracranial pressure-targeted therapy.

OBJECT The authors prospectively studied the occurrence of clinical and nonclinical electroencephalographically verified seizures during treatment with an intracranial pressure (ICP)-targeted protocol in patients with traumatic brain injury (TBI). METHODS All patients treated for TBI at the Department of Neurosurgery, University Hospital Umeå, Sweden, were eligible for the study. The inclusion was consecutive and based on the availability of the electroencephalographic (EEG) monitoring equipment. Patients were included irrespective of pupil size, pupil reaction, or level of consciousness as long as their first measured cerebral perfusion pressure was > 10 mm Hg. The patients were treated in a protocol-guided manner with an ICP-targeted treatment based on the Lund concept. The patients were continuously sedated with midazolam, fentanyl, propofol, or thiopental, or combinations thereof. Five-lead continuous EEG monitoring was performed with the electrodes at F3, F4, P3, P4, and a midline reference. Sensitivity was set at 100 muV per cm and filter settings 0.5-70 Hz. Amplitude-integrated EEG recording and relative band power trends were displayed. The trends were analyzed offline by trained clinical neurophysiologists. RESULTS Forty-seven patients (mean age 40 years) were studied. Their median Glasgow Coma Scale score at the time of sedation and intubation was 6 (range 3-15). In 8.5% of the patients clinical seizures were observed before sedation and intubation. Continuous EEG monitoring was performed for a total of 7334 hours. During this time neither EEG nor clinical seizures were observed. CONCLUSIONS Our protocol-guided ICP targeted treatment seems to protect patients with severe TBI from clinical and subclinical seizures and thus reduces the risk of secondary brain injury.

Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine

Abstract Objective. Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endothelial dysfunction. The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls. Methods. A prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained 3 months later. A single blood sample for ADMA was collected from age- and sex-matched healthy controls (n = 40, two for each case). Results. CRP increased significantly from day 2; 16 (Confidence interval (CI) 10–23) mg/L to day 4; 84 (CI 47–120) mg/L, (p < 0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17–0.27) μmol/L, to day 7; 0.37 (CI 0.21–0.54) μmol/L, p < 0.01. ADMA remained elevated at a 3-month follow-up: 0.36 (CI 0.31–0.42) μmol/L. ADMA in the first sample from the patients (day 1–3); 0.25 (CI 0.19–0.30) μmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20–0.31), p > 0.05. Conclusion. After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated 3 months later.

Prostacyclin treatment and clinical outcome in severe traumatic brain injury patients managed with an ICP-targeted therapy: a prospective study.

Objective: To prospectively assess clinical outcome in patients with severe traumatic brain injury (sTBI) managed according to an ICP-targeted programme as well as additional treatment with prostacyclin. Materials and methods: Inclusion criteria were GCS ≤8, age 15–70 years, first recorded cerebral perfusion pressure (CPP) > 10 mm Hg. Exclusion criteria were pregnancy, breastfeeding or penetrating brain injury. The patients were treated using the same ICP-guided protocol, with one group randomized to receive prostacyclin in a low dose (0.5 ng kg−1 min−1). The clinical outcome was prospectively assessed at 3, 6, 12, 18 and 24 months using structured interviews. Results: Forty-eight patients were included, mean age 35.5 years, median GCS 6 (3–8), 69% were multi-traumatized. Mortality at 3 months was 12.5%. Median Glasgow Outcome Scale (GOS) at all follow-up points was 4. Favourable outcome (GOS 4–5) at 3 months was 52%, at 24 months 64%. Favourable outcome increased over time. There was a statistically significant association between GOS, GCS at admission and age. Higher ICPmax was associated with worse outcome. Conclusion: With this treatment protocol, a low number of deaths and a high number of favourable outcomes in sTBI were observed. Prostacyclin in this low dose does not seem to improve the outcome. ICPmax is a positive predictor of worse outcome. Higher GCS at admission and lower age are correlated to better outcome.