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Fartein Velle, Anders Lewén, Timothy Howells, Per Enblad and Pelle Nilsson

OBJECTIVE

Refractory intracranial pressure (ICP) hypertension following traumatic brain injury (TBI) is a severe condition that requires potentially harmful treatment strategies such as barbiturate coma. However, the use of barbiturates may be restricted due to concerns about inducing multiorgan system complications related to the therapy. The purpose of this study was to evaluate the outcome and occurrence of treatment-related complications to barbiturate coma treatment in children with refractory intracranial hypertension (RICH) due to TBI in a modern multimodality neurointensive care unit (NICU).

METHODS

The authors conducted a retrospective cohort study of 21 children ≤ 16 years old who were treated in their NICU between 2005 and 2015 with barbiturate coma for RICH following TBI. Demographic and clinical data were acquired from patient records and physiological data from digital monitoring system files.

RESULTS

The median age of these 21 children was 14 years (range 2–16 years) and at admission the median Glasgow Coma Scale score was 7 (range 4–8). Barbiturate coma treatment was added due to RICH at a median of 46 hours from trauma and had a median duration of 107 hours. The onset of barbiturate coma resulted in lower ICP values, lower pulse amplitudes on the ICP curve, and decreased amount of A-waves. No major disturbances in blood gases, liver and kidney function, or secondary insults were observed during this period. Outcome 1 year later revealed a median Glasgow Outcome Scale score of 5 (good recovery), however on the King’s Outcome Scale for Childhood Head Injury, the median was 4a (moderate disability).

CONCLUSIONS

The results of this study indicate that barbiturate coma, when used in a modern NICU, is an effective means of lowering ICP without causing concomitant severe side effects in children with RICH and was compatible with good long-term outcome.

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Sami Abu Hamdeh, Niklas Marklund, Anders Lewén, Tim Howells, Raili Raininko, Johan Wikström and Per Enblad

OBJECTIVE

Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in patients with DAI.

METHODS

Fifty-two patients with severe TBI (median age 24 years, range 9–61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2*-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression.

RESULTS

All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%–13%, p = 0.004) and young age (−0.2% of GMT with ICP > 20 mm Hg, 95% CI −0.07% to −0.3%, p = 0.002) were associated with increased ICP.

CONCLUSIONS

Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.

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Lennart Persson, Johann Valtysson, Per Enblad, Per-Erik Wärme, Kristina Cesarini, Anders Lewén and Lars Hillered

✓ The authors have developed a method for routine monitoring of disturbances in brain energy metabolism and extracellular levels of excitatory amino acids using intracerebral microdialysis in 10 patients with subarachnoid hemorrhage. Microdialysis was conducted for periods ranging from 6 to 11 days after ictus. Altogether, 16,054 chemical analyses from 1647 dialysate samples were performed. Concentrations of the energy-related substances lactate, pyruvate, glucose, and hypoxanthine were measured, and the lactate/pyruvate ratio was calculated. The excitatory amino acids glutamate and aspartate were measured. The microdialysis data were matched with computerized tomography findings, clinical course, and outcome. The results support the concepts that microdialysis is a promising tool for chemical monitoring of the human brain and that extracellular fluid levels of lactate, lactate/pyruvate ratio, glucose, hypoxanthine, and glutamate are useful markers of disturbances in brain energy metabolism in neurointensive care patients. These results have generated a working hypothesis that the pattern of these extracellular markers may help differentiate between various causes of energy perturbations, such as hypoxia and different degrees of ischemia. The correlation between the dialysate levels of excitatory amino acids and outcome supports the concept of glutamate receptor overactivation in acute human brain injury.

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Henrik Engquist, Anders Lewén, Lars Hillered, Elisabeth Ronne-Engström, Pelle Nilsson, Per Enblad and Elham Rostami

OBJECTIVE

Despite the multifactorial pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), augmentation of cerebral blood flow (CBF) is still considered essential in the clinical management of DCI. The aim of this prospective observational study was to investigate cerebral metabolic changes in relation to CBF during therapeutic hypervolemia, hemodilution, and hypertension (HHH) therapy in poor-grade SAH patients with DCI.

METHODS

CBF was assessed by bedside xenon-enhanced CT at days 0–3, 4–7, and 8–12, and the cerebral metabolic state by cerebral microdialysis (CMD), analyzing glucose, lactate, pyruvate, and glutamate hourly. At clinical suspicion of DCI, HHH therapy was instituted for 5 days. CBF measurements and CMD data at baseline and during HHH therapy were required for study inclusion. Non-DCI patients with measurements in corresponding time windows were included as a reference group.

RESULTS

In DCI patients receiving HHH therapy (n = 12), global cortical CBF increased from 30.4 ml/100 g/min (IQR 25.1–33.8 ml/100 g/min) to 38.4 ml/100 g/min (IQR 34.2–46.1 ml/100 g/min; p = 0.006). The energy metabolic CMD parameters stayed statistically unchanged with a lactate/pyruvate (L/P) ratio of 26.9 (IQR 22.9–48.5) at baseline and 31.6 (IQR 22.4–35.7) during HHH. Categorized by energy metabolic patterns during HHH, no patient had severe ischemia, 8 showed derangement corresponding to mitochondrial dysfunction, and 4 were normal. The reference group of non-DCI patients (n = 11) had higher CBF and lower L/P ratios at baseline with no change over time, and the metabolic pattern was normal in all these patients.

CONCLUSIONS

Global and regional CBF improved and the cerebral energy metabolic CMD parameters stayed statistically unchanged during HHH therapy in DCI patients. None of the patients developed metabolic signs of severe ischemia, but a disturbed energy metabolic pattern was a common occurrence, possibly explained by mitochondrial dysfunction despite improved microcirculation.

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Elham Rostami, Henrik Engquist, Timothy Howells, Ulf Johnson, Elisabeth Ronne-Engström, Pelle Nilsson, Lars Hillered, Anders Lewén and Per Enblad

OBJECTIVE

Delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is one of the major contributors to poor outcome. It is crucial to be able to detect early signs of DCI to prevent its occurrence. The objective of this study was to determine if low cerebral blood flow (CBF) measurements and pathological microdialysis parameters measured at the bedside can be observed early in patients with SAH who later developed DCI.

METHODS

The authors included 30 patients with severe SAH. The CBF measurements were performed at Day 0–3 after disease onset, using bedside xenon-CT. Interstitial glucose, lactate, pyruvate, glycerol, and glutamate were measured using microdialysis.

RESULTS

Nine of 30 patients developed DCI. Patients with DCI showed significantly lower global and regional CBF, and lactate was significantly increased in these patients. A high lactate/pyruvate ratio was also detected in patients with DCI.

CONCLUSIONS

Early low CBF measurements and a high lactate and lactate/pyruvate ratio may be early warning signs of the risk of developing DCI. The clinical value of these findings needs to be confirmed in larger studies.