Asita Sarrafzadeh

Bedside microdialysis: a tool to monitor cerebral metabolism in subarachnoid hemorrhage patients?

ObjectiveTo analyze the time course and changes of cerebral microdialysis parameters after aneurysmal subarachnoid hemorrhage (SAH) in respect to the clinical course (asymptomatic, delayed, and acute ischemic neurologic deficits) to evaluate the method of bedside microdialysis in these patients. DesignProspective, controlled study during a 3-yr period. SettingNeurosurgical intensive care unit at a primary level university hospital, supervised and staffed by members of both the department of neurosurgery and the department of anesthesiology and intensive care medicine. PatientsNinety-seven patients (51 females/21 males; 52 ± 13 yrs; World Federation of Neurological Surgeons Scale grades 0–5) after aneurysmatic SAH. Measurements and Main ResultsA microdialysis catheter (CMA 100) was inserted into the region most likely to be affected by vasospasm directly after aneurysm clipping, connected to a pump, and perfused with Ringer solution (0.3 &mgr;L/min). The dialysates were collected hourly and analyzed at the bedside for glucose, lactate, lactate-pyruvate ratio, glutamate, and glycerol (CMA 600). Patients were classified according to clinical presentation as being asymptomatic or having acute (AIND) or delayed (DIND) ischemic neurologic deficits. DIND patients (n = 18) had significantly higher lactate and glutamate concentrations on days 1–8 post-SAH and a higher lactate-pyruvate ratio on days 3–8 post-SAH compared with asymptomatic patients (n = 57;p < .025). Glucose and glycerol levels did not differ in asymptomatic and DIND patients. AIND patients (n = 22) had the worst metabolic pattern: the extracellular glucose concentration was low, whereas the lactate, lactate-pyruvate ratio, glutamate, and glycerol levels were significantly elevated compared with asymptomatic and DIND patients. In 83% of the DIND patients, the changes in metabolites indicative of cerebral ischemia preceded the onset of symptomatic vasospasm. All DIND patients clinically improved in their Glasgow Coma Scale scores with induced hypertension, intentional hypervolemia, and/or hemodilution therapy (p = .01). ConclusionCerebral bedside microdialysis is a safe and promising technique for monitoring (impending) regional cerebral ischemia. The dialysate changes can indicate early the onset of delayed neurologic deterioration and are in good accordance with the clinical course of SAH patients. In the future, this technique may be used to monitor the efficacy of the intensive care therapy of these patients.

Multimodal monitoring in patients with head injury: evaluation of the effects of treatment on cerebral oxygenation.

BACKGROUND Recently, invasive intensive care unit monitoring of cerebral oxygenation has become feasible. The purpose of this study was to investigate the effects of standard therapeutic interventions used in the treatment of intracranial hypertension on cerebral oxygenation and other physiologic parameters in comatose patients. METHODS In the neurosurgical intensive care unit, Ptio2, and jugular bulb oxygen saturation (Sjvo2), arterial blood pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were prospectively studied (0.1 Hz acquisition rate) with a multimodal monitoring system in 21 patients with severe traumatic brain injury during various treatment modalities: dopamine and mannitol infusion, head positioning, and induced arterial hypocapnia. RESULTS For baseline CPP values below 40 mm Hg, dopamine infusion was more effective in decreasing ICP and improving Ptio2 and Sjvo2 than for initial CPP values above 60 mm Hg. Treatment with mannitol, although improving CPP and lowering ICP, did not affect Ptio2 and Sjvo2. CPP in this group, however, was always above 60 mm Hg. Forced hyperventilation to an end-tidal Pco2 of 21 mm Hg normalized ICP and CPP, but significantly reduced cerebral oxygenation. CONCLUSION A CPP > 60 mm Hg emerges as the crucial factor guaranteeing sufficient brain oxygenation. Any intervention used to further elevate CPP does not improve cerebral oxygenation, to the contrary, forced hyperventilation even bears the risk of inducing brain ischemia.

Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage A Correlative Microdialysis-PET Study

Background and Purpose— Cerebral microdialysis (MD) is discussed as a technique for detection of cerebral ischemia in subarachnoid hemorrhage; however, clinical data on cerebral blood flow (CBF) are limited in these patients. The main objective of this study was to investigate whether pathological MD parameters reflect a reduced regional CBF (rCBF) determined by 15O-H2O PET. Methods— Thirteen subarachnoid hemorrhage patients (age, 48.7±15.0 years; World Federation of Neurological Surgeons grade 1 to 5) were studied. Extracellular glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol levels were analyzed hourly. rCBF was determined in the volume of interest of the MD catheter and all vascular territories. MD values were correlated to rCBF on the day of PET. Then, MD concentrations of asymptomatic versus ischemic phases (3-day medians) were analyzed. Results— In symptomatic patients (n=10), rCBF was significantly lower compared with controls (n=3, P =0.048). Glutamate correlated best with rCBF (r =−0.66; P =0.014), followed by glycerol (r =−0.62; P =0.021). The L/P ratio was most sensitive (0.82) and specific (1.0) in indicating symptoms of ischemia, but only during longer periods of ischemia. Conclusions— rCBF correlates best with glutamate, followed by glycerol, whereas the L/P ratio is sensitive only after longer periods of ischemia. Clinically relevant regional metabolic derangements occur already above an rCBF of 20 mL·100 g−1·min−1. Future research should focus on identifying alternative causes of metabolic derangement in subarachnoid hemorrhage patients and optimal treatment management in these patients.

Secondary insults in severe head injury: Do multiply injured patients do worse?

Objectives To study the occurrence of secondary insults and the influence of extracranial injuries on cerebral oxygenation and outcome in patients with closed severe head injury (Glasgow Coma Scale score ≤8). Design Two-year prospective, clinical study. Setting Two intensive care units in a level III trauma center. Patients We studied 119 patients. Eighty patients had severe head injury and were divided into two categories: “isolated” severe head injury patients (n = 36, Injury Severity Score <30), and severe head injury patients with associated extracranial injuries (n = 44, Injury Severity Score >29). Thirty-nine patients with extracranial injuries and no head injury served as the control group. Interventions After patients were admitted to the intensive care unit, we began continuous multimodal cerebral monitoring of intracranial pressure, mean arterial blood pressure, cerebral perfusion pressure, end-tidal Co2 , brain tissue Po2 (Licox), jugular bulb oxyhemoglobin saturation in severe head injury patients, and mean arterial blood pressure in the control group. Targets of management included intracranial pressure <20 mm Hg, cerebral perfusion pressure >60 mm Hg, Paco2 > 30 mm Hg, control of cerebral oxygenation, and delayed surgery for non-life-threatening extracranial lesions. Measurements and Main Results Data were analyzed for critical thresholds. The occurrence of secondary insults (intracranial pressure >20 mm Hg, mean arterial blood pressure <70 mm Hg, cerebral perfusion pressure <60 mm Hg, end-tidal Co2 <30 torr, brain tissue Po2 <10 torr, jugular bulb oxyhemoglobin saturation <50%) was comparable in patients with isolated severe head injury and those with severe head injury with associated extracranial lesions (Abbreviated Injury Scale score ≤5). The duration of intracranial hypertension and arterial hypotension significantly correlated with an unfavorable outcome, independent of the Injury Severity Score. In patients with severe head injury, 1-yr outcome was 29% dead or vegetative, 17% severely disabled, and 54% moderate or good outcome. This was similar to patients with severe head injury and extracranial injuries (31% dead or vegetative, 14% severely disabled, and 56% moderate or good outcome) and was independent of the Injury Severity Score. Patients with no head injury had less secondary insults (mean arterial blood pressure <70 mm Hg, p < .01) and a better outcome compared with both severe head injury groups (p < .044). Conclusions In patients with severe head injury who have targeted management including intracranial pressure- and cerebral perfusion pressure-guided therapy and delayed surgery for extracranial lesions, the occurrence of secondary insults in the intensive care unit and long-term neurological outcome were comparable and independent of the presence of extracranial lesions (Abbreviated Injury Severity level ≤5). A severe head injury is still a major contributor predicting an unfavorable outcome in multiply injured patients.

Preliminary Evidence That Ketamine Inhibits Spreading Depolarizations in Acute Human Brain Injury

Background and Purpose— Spreading depolarizations, characterized by large propagating, slow potential changes, have been demonstrated with electrocorticography in patients with cerebral hemorrhage and ischemic stroke. Whereas spreading depolarizations are harmless under normal conditions in animals, they cause or augment damage in the ischemic brain. A fraction of spreading depolarizations is abolished by N-methyl-d-aspartate receptor antagonists. Summary of Case— In 2 patients with severe acute brain injury (traumatic and spontaneous intracranial hemorrhage), spreading depolarizations were inhibited by the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine. This restored electrocorticographic activity. Conclusions— These anecdotal electrocorticographic findings suggest that ketamine has an inhibitory effect on spreading depolarizations in humans. This is of potential interest for future neuroprotective trials.

Clusters of Spreading Depolarizations Are Associated With Disturbed Cerebral Metabolism in Patients With Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— We studied the dynamics of extracellular brain tissue concentrations of glucose, lactate, pyruvate, and glutamate during the occurrence of spreading depolarizations (SDs) in patients with aneurysmal subarachnoid hemorrhage. Methods— In this prospective observational study, patients with aneurysmal subarachnoid hemorrhage received multimodal cerebral monitoring, including intracranial pressure, cerebral microdialysis, and subdural electrocorticography. Results— Seven of the 17 recruited patients had intracerebral hemorrhage, acute ischemia and severe brain oedema leading to acute ischemic neurological deficits associated with early disturbance of metabolism at the recording site. They displayed a total of 130 SDs. The remaining 10 patients without acute ischemic neurological deficits exhibited 138 single SDs and 68 SDs in clusters. In patients without acute ischemic neurological deficits, clustered SDs were associated with a significant transient decrease in glucose and increase in lactate compared with baseline during the first 140 minutes after SDs. Moreover, the number of clustered SDs correlated with the outcome (R=−0.659; P<0.01). Conclusion— SDs can propagate in nonischemic human brain tissue. Clusters of SDs are related to metabolic changes suggestive of ongoing secondary damage in primarily nonischemic brain tissue.

Impact of hyperglycemia on neurological deficits and extracellular glucose levels in aneurysmal subarachnoid hemorrhage patients.

Abstract Objective: Hyperglycemia after aneurysmal subarachnoid hemorrhage (SAH) is associated with serious complications. Blood glucose may indicate a target for therapy to prevent delayed ischemic neurological deficits (DIND) and improve outcome. The objective of this study was to investigate energy metabolism in the extracellular/cerebrospinal fluid and blood in relation to outcome. Methods: Prospective non-randomized study was carried out in the intensive care unit (ICU) of university hospital (n = 170 aneurysmal SAH patients, age: 51.0 ± 12.6 years old). Following approval by the ethics committee, a microdialysis catheter was inserted into the vascular territory of the aneurysm after clipping. Patients were studied for 165 ± 84 hours and classified according to the presence of neurological symptoms as asymptomatic (n = 66) and symptomatic (n = 104): acute focal neurological deficits (AFND, n = 61) and delayed ischemic neurological deficits (DIND, n = 43). The microdialysates were analysed hourly for energy metabolites. Daily morning blood glucose and cerebrospinal fluid (CSF) levels (glucose and lactate) were determined. Six-month Glasgow outcome scale (GOS) was assessed. Results: Hyperglycemia on admission and high blood glucose levels on the following days were significantly related to the presence of symptoms, most pronounced in patients with poor outcome (p<0.05). In symptomatic patients (high blood glucose), the lowest extracellular fluid (ECF) glucose concentrations were found, most pronounced in the AFND group (1.0 ± 1.2 mmol/l). The anaerobic metabolites lactate, lactate/pyruvate ratio (LPR) and lactate/glucose ratio (LGR) were higher in symptomatic patients (p<0.001) indicating cerebral metabolic distress. CSF concentrations of glucose and lactate were of no specific value. Conclusion: This study confirms the relevance of hyperglycemia to neurological outcome in SAH patients. Cerebral glucose was significantly lower in AFND patients despite hyperglycemic blood levels. More detailed works are necessary to select risk patients for optimized targeted therapy to avoid insulin-induced cerebral metabolic crisis.

Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachnoid hemorrhage

Abstract Objectives: The pathogenesis of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) is multi-factorial and not completely elucidated. Matrix metalloproteinase-9 (MMP-9) might participate in wall remodeling leading to luminal narrowing. The authors investigated MMP-9 concentration in brain extracellular fluid of aSAH patients and assessed whether this enzyme could have a predictive value for the risk of DCI. Methods: Patients were classified according to the grading of the World Federation of Neurological Surgeons (WFNS) in low- and high-grade patients (WFNS = 1–3, n = 9 and WFNS = 4–5, n = 12, respectively). Cerebral microdialysis probes were placed in brain parenchyma of the respective vascular territory of the aneurysm in 21 consecutive aSAH patients, enrolled in a prospective study on inflammation. Microdialysis samples, collected daily from day 0 until day 8 after aSAH, were retrospectively analyzed for MMP-9 by zymography. Results: Initial concentration of the MMP-9 proform (pro-MMP-9) was significantly higher in high-grade patients as compared to low-grade patients. Furthermore, initial pro-MMP-9 concentration in patients with DCI was seven-fold higher than in asymptomatic patients. Pro-MMP-9 values greater than or equal to 0·27 pg/μl showed 83% sensitivity and 63% specificity in predicting vasospasm. The mature form of the MMP-9 could be preferentially detected in patients with DCI but was usually low. Discussion: The pro and mature forms of MMP-9 were released locally in the brain after aSAH. Pro-MMP-9 release was related to WFNS grade severity. This protease, considered as playing a critical role in endothelial basal membrane damage, may contribute to the inflammatory processes leading to arterial narrowing.

Augmented reality-assisted skull base surgery

Neuronavigation is widely considered as a valuable tool during skull base surgery. Advances in neuronavigation technology, with the integration of augmented reality, present advantages over traditional point-based neuronavigation. However, this development has not yet made its way into routine surgical practice, possibly due to a lack of acquaintance with these systems. In this report, we illustrate the usefulness and easy application of augmented reality-based neuronavigation through a case example of a patient with a clivus chordoma. We also demonstrate how augmented reality can help throughout all phases of a skull base procedure, from the verification of neuronavigation accuracy to intraoperative image-guidance.

Monitoring in Neurointensive Care – The Challenge to Detect Delayed Cerebral Ischemia in High-Grade Aneurysmal SAH

Delayed cerebral ischemia (DCI) is a feared and significant medical complication following aneurysmal subarachnoid hemorrhage (aSAH). It occurs in about 30% of patients surviving the initial hemorrhage, mostly between days 4 and 10 after aSAH. Clinical deterioration attributable to DCI is a diagnosis of exclusion and especially difficult to diagnose in patients who are comatose or sedated. The latter are typically patients with a high grade on the World Federation of Neurosurgical Societies scale (WFNS grade 4–5), who represent approximately 40–70% of the patient population with ruptured aneurysms. In this group of patients, the incidence of DCI is often underestimated and higher when compared to low WFNS grade patients. To overcome difficulties in diagnosing DCI, which is especially relevant in sedated and comatose patients, the article reports the most recent recommendation for definition of DCI and discusses their advantages and problematic issues in neurocritical care practice. Finally, appropriate neuromonitoring techniques and their clinical impact in high-grade SAH patients are summarized.