Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury – a study of cerebral blood flow and metabolism

Summary Objective. To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO₂), glucose (CMRGlc) and lactate (CMRLct). Methods. Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO₂ from 36 ± 4 to 32 ± 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO₂, CMRGlc and CMRLct. Results. Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml·100 gr⁻¹·min⁻¹ were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO₂, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. Conclusions. Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.     

Monitoring of cerebral blood flow and metabolism in traumatic brain injury

The aim of the present study was to investigate the course of cerebral blood flow (CBF) and metabolism in traumatic brain injury (TBI) patients and to specifically characterize the changes in lactate and glucose indices in the acute post-traumatic period with regard to neurological condition and functional outcome. For this purpose, 55 consecutive TBI patients (mean age 37 +/- 17 years, mean GCS 6.8 +/- 3.2) were prospectively and daily evaluated. Global CBF, cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc), and lactate (CMRLct) were calculated using arterial jugular differences. In all patients, CBF was moderately decreased during the first 24 h in comparison with normal subjects although this relative oligemia was more pronounced in patients with poor outcome (p = 0.0007). Both CMRO2 and CMRGlc were significantly depressed and correlated to outcome (p < 0.0001, p = 0.0088). CMRLct analysis revealed positive values (lactate uptake) during the first 48 h, especially in patients with favorable outcome. Both CMRO2 and CMRLct correlated with GCS (p = 0.0001, p = 0.0205). CMRLct levels showed an opposite correlation with CBF in patients with favorable and poor outcome. In the former group, correlation analysis exhibited a negative slope with evidence for increasing lactate uptake associated with lower CBF values (r = -0.1940, p = 0.0242). On the contrary, in patients with adverse outcome, CMRLct values demonstrated a weak though opposite correlation with CBF (r = 0.0942, p = 0.2733). The present data emphasize the clinical significance of monitoring of cerebral blood flow and metabolism in TBI and provide evidence for metabolic coupling between astrocytes and neurons.     

Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury.

OBJECT: Recently, concern has been raised that hyperventilation following severe traumatic brain injury (TBI) could lead to cerebral ischemia. In acute ischemic stroke, in which the baseline metabolic rate is normal, reduction in cerebral blood flow (CBF) below a threshold of 18 to 20 ml/100 g/min is associated with energy failure. In severe TBI, however, the metabolic rate of cerebral oxygen (CMRO2) is low. The authors previously reported that moderate hyperventilation lowered global hemispheric CBF to 25 ml/100 g/min but did not alter CMRO2. In the present study they sought to determine if hyperventilation lowers CBF below the ischemic threshold of 18 to 20 ml/100 g/ min in any brain region and if those reductions cause energy failure (defined as a fall in CMRO2). METHODS: Two groups of patients were studied. The moderate hyperventilation group (nine patients) underwent hyperventilation to PaCO2 of 30 +/- 2 mm Hg early after TBI, regardless of intracranial pressure (ICP). The severe hyperventilation group (four patients) underwent hyperventilation to PaCO2 of 25 +/- 2 mm Hg 1 to 5 days postinjury while ICP was elevated (20-30 mm Hg). The ICP, mean arterial blood pressure, and jugular venous O2 content were monitored, and cerebral perfusion pressure was maintained at 70 mm Hg or higher by using vasopressors when needed. All data are given as the mean +/- standard deviation unless specified otherwise. The moderate hyperventilation group was studied 11.2 +/- 1.6 hours (range 8-14 hours) postinjury, the admission Glasgow Coma Scale (GCS) score was 5.6 +/- 1.8, the mean age was 27 +/- 9 years, and eight of the nine patients were men. In the severe hyperventilation group, the admission GCS score was 4.3 +/- 1.5, the mean age was 31 +/- 6 years, and all patients were men. Positron emission tomography measurements of regional CBF, cerebral blood volume, CMRO2, and oxygen extraction fraction (OEF) were obtained before and during hyperventilation. In all 13 patients an automated search routine was used to identify 2.1-cm spherical nonoverlapping regions with CBF values below thresholds of 20, 15, and 10 ml/ 100 g/min during hyperventilation, and the change in CMRO2 in those regions was determined. In the regions in which CBF was less than 20 ml/100 g/min during hyperventilation, it fell from 26 +/- 6.2 to 13.7 +/- 1 ml/ 100 g/min (p < 0.0001), OEF rose from 0.31 to 0.59 (p < 0.0001), and CMRO2 was unchanged (1.12 +/- 0.29 compared with 1.14 +/- 0.03 ml/100 g/min; p = 0.8). In the regions in which CBF was less than 15 ml/100 g/min during hyperventilation, it fell from 23.3 +/- 6.6 to 11.1 +/- 1.2 ml/100 g/min (p < 0.0001), OEF rose from 0.31 to 0.63 (p < 0.0001), and CMRO2 was unchanged (0.98 +/- 0.19 compared with 0.97 +/- 0.23 ml/100 g/min; p = 0.92). In the regions in which CBF was less than 10 ml/100 g/min during hyperventilation, it fell from 18.2 +/- 4.5 to 8.1 +/- 0 ml/100 g/min (p < 0.0001), OEF rose from 0.3 to 0.71 (p < 0.0001), and CMRO2 was unchanged (0.78 +/- 0.26 compared with 0.84 +/- 0.32 ml/100 g/min; p = 0.64). CONCLUSIONS: After severe TBI, brief hyperventilation produced large reductions in CBF but not energy failure, even in regions in which CBF fell below the threshold for energy failure defined in acute ischemia. Oxygen metabolism was preserved due to the low baseline metabolic rate and compensatory increases in OEF; thus, these reductions in CBF are unlikely to cause further brain injury.     

Effect of graded hyperventilation on cerebral metabolism in a cisterna magna blood injection model of subarachnoid hemorrhage in rats

In subarachnoid hemorrhage (SAH) with cerebrovascular instability, hyperventilation may induce a risk of inducing or aggravating cerebral ischemia. We measured cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRglc), and lactate (CMRlac) at different PaCO2 levels after experimental SAH in rats (injection of 0.07 mL of autologous blood into the cisterna magna). Four groups of Sprague-Dawley male rats were studied at predetermined PaCO2 levels: group A: normocapnia (5.01-5.66 kPa [38.0-42.0 mm Hg]); group B: slight hyperventilation (4.34-5.00 kPa [32.5-37.5 mm Hg]); group C: moderate hyperventilation (3.67-4.33 kPa [27.5-32.4 mm Hg]); group D: profound hyperventilation (3.00-3.66 kPa [22.5-27.4 mm Hg]). Each of the four groups included eight rats with SAH and eight sham-operated controls. CBF was determined by the intracarotid Xe method; CMRo2, CMRglc, and CMRlac were obtained by cerebral arteriovenous differences. In both SAH rats and controls, hyperventilation decreased CBF in proportion to the decrement in PaCO2 without affecting either CMRO2, CMRglc, or CMRlac. In groups C and D, CBF decreased by 20%-35%, but CMRs were maintained by a compensatory increase in oxygen extraction fraction (OEF). The results show that even profound hyperventilation in this model of SAH is associated with an adequate increase in OEF so that CMRs of oxygen, glucose, and lactate remain similar to levels observed in normocapnic conditions.     

Comparison of effects of equiosmolar doses of mannitol and hypertonic saline on cerebral blood flow and metabolism in traumatic brain injury

The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4?mL/kg; n=25 patients) or HTS 7.5% (2?mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120?min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.     

Effects of mannitol bolus administration on intracranial pressure, cerebral extracellular metabolites, and tissue oxygenation in severely head-injured patients

BACKGROUND: Osmotic agents are widely used to lower elevated intracranial pressure (ICP). However, little data are available regarding cerebral oxygenation and metabolism in the traumatized brains studied under clinical conditions. The present prospective, open-labeled clinical study was designed to investigate whether administration of mannitol, with the aim of reducing moderate intracranial hypertension, improves cerebral metabolism and oxygenation in patients after severe traumatic brain injury (TBI). METHODS: Multimodal cerebral monitoring (MCM), consisting of intraparenchymal ICP, tissue oxygenation (ptiO2), and micro dialysis measurements was initiated in six male TBI patients (mean age 45 years; Glasgow Coma Scale score <9). A total of 14 mannitol boli (20%, 0.5g/kg, 20 minutes infusion time) were administered to treat ICP exceeding 20 mm Hg (2.7 kPa). Temporal alterations determined by MCM after mannitol infusions were recorded for 120 minutes. Microdialysates were assayed immediately for extracellular glucose, lactate, pyruvate, and glutamate concentrations. RESULTS: Elevated ICP was successfully treated in all cases. This effect was maximal 40 minutes after start of infusion (25 +/- 6 mm Hg [3.3 +/- 0.8 kPa] to 17 +/- 3 mm Hg [2.3 +/- 0.4 kPa], p < 0.05) and lasted up to 100 minutes. Cerebral ptiO2 remained unaffected (21 +/- 5 mm Hg [2.8 +/- 0.7 kPa] to 23 +/- 6 mm Hg [3.1 +/- 0.8 kPa], n.s.). Microdialysate concentrations of all analytes rose unspecifically by 10% to 40% from baseline, reaching maximum concentrations 40 to 60 minutes after start of the infusion. CONCLUSIONS: Mannitol efficiently reduces increased ICP. At an ICP of up to 30 mm Hg [4 kPa] it does not affect cerebral oxygenation. Unspecific increases of extracellular fluid metabolites can be explained by transient osmotic dehydration. Additional mechanisms, such as increased cerebral perfusion and blood volume, might explain an accelerated return to baseline.     

A pig model with secondary increase of intracranial pressure after severe traumatic brain injury and temporary blood loss

There is a lack of animal models of traumatic brain injury (TBI) that adequately simulate the longterm changes in intracranial pressure (ICP) increase following clinical TBI. We therefore reproduced the clinical scenario in an animal model of TBI and studied long-term postinjury changes in ICP and indices of brain injury. After induction of anesthesia, juvenile piglets were randomly traumatized using fluid-percussion injury (FPI) to induce either moderate (mTBI = 6 pigs: 3.2 +/- 0.6 atm) or severe (sTBI = 7 pigs: 4.1 +/- 1.0 atm) TBI. Injury was followed by a 30% withdrawal of blood volume. ICP and systemic hemodynamic were monitored continuously. Repeated measurements of global cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were performed at baseline, at the end of blood withdrawal, after volume replacement, and at 8 and 24 h postinjury. Histological and immunocytochemical studies have also performed. ICP peaked immediately following FPI (mTBI: 33 +/- 16 mm Hg; sTBI: 47 +/- 14 mm Hg, p < 0.05) in both groups. In the sTBI group, we noted a second peak at 5 +/- 1.5 h postinjury. This second ICP peak was accompanied by a 50% reduction in CBF (44 +/- 31 mL . min . 100 g(-1)) and CMRO(2) (2.5 +/- 2.0 mL . min . 100 g(1)). Moderate TBI typically resulted in focal pathological change whereas sTBI caused more diffuse change, particularly in terms of the ensuing axonal damage. We thus describe an animal model of severe TBI with a reproducible secondary ICP increase accompanied by patterns of diffuse brain damage. This model may be helpful in the study of pathogenetic relevance of concomitant affections and verify new therapeutic approaches in severe TBI.     

Cerebral blood flow, vasoreactivity, and oxygen consumption during barbiturate therapy in severe traumatic brain lesions

Mean hemispheric cerebral blood flow (CBF) and intracranial pressure (ICP) were measured in 19 severely head-injured patients treated with barbiturate coma. The CBF was calculated from the clearance of tracer substance monitored by extracranial scintillation detectors after intravenous administration of xenon-133. In 11 of the patients cerebral arteriovenous oxygen differences were measured simultaneously. In all patients the effects of pronounced hyperventilation were recorded prior to initiation of barbiturate treatment. A normal CBF response to hyperventilation (delta CBF/delta PaCO2 greater than or equal to 1) was obtained in eight patients. In these patients induction of barbiturate coma was accompanied by physiological decreases in CBF and in the calculated cerebral metabolic rate of oxygen (CMRO2); they also exhibited a rapid and lasting decrease in ICP. A decreased or an abolished CO2 reactivity was recorded (delta CBF/delta PaCO2 less than 1) in 11 patients. In 10 of these 11 patients the physiological decreases in CBF and CMRO2 were not obtained during barbiturate treatment and the decrease in ICP was transitory. This study demonstrates a correlation between cerebral vasoreactivity, physiological effects of barbiturate therapy, and clinical outcome.     

Cerebral circulation and metabolism in the acute stage of subarachnoid hemorrhage

OBJECT: The mechanism of reduction of cerebral circulation and metabolism in patients in the acute stage of aneurysmal subarachnoid hemorrhage (SAH) has not yet been fully clarified. The goal of this study was to elucidate this mechanism further. METHODS: The authors estimated cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), O2 extraction fraction (OEF), and cerebral blood volume (CBV) preoperatively in eight patients with aneurysmal SAH (one man and seven women, mean age 63.5 years) within 40 hours of onset by using positron emission tomography (PET). The patients' CBF, CMRO2, and CBF/CBV were significantly lower than those in normal control volunteers. However, OEF and CBV did not differ significantly from those in control volunteers. The significant decrease in CBF/CBV, which indicates reduced cerebral perfusion pressure, was believed to be caused by impaired cerebral circulation due to elevated intracranial pressure (ICP) after rupture of the aneurysm. In two of the eight patients, uncoupling between CBF and CMRO2 was shown, strongly suggesting the presence of cerebral ischemia. CONCLUSIONS: The initial reduction in CBF due to elevated ICP, followed by reduction in CMRO, at the time of aneurysm rupture may play a role in the disturbance of CBF and cerebral metabolism in the acute stage of aneurysmal SAH.     

The Brain Trauma Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Hyperventilation

Chronic prophylactic hyperventilation therapy should be avoided during the first 5 days after severe TBI and particularly during the first 24 h. CBF measurements in patients with severe TBI demonstrate that blood flow early after injury is low and strongly suggest that in the first few hours after injury the absolute values approach those consistent with ischemia. These findings are corroborated by AVdO2 and SjO2 and brain tissue O2 measurements. Hyperventilation will reduce CBF values even further, but will not consistently cause a reduction of ICP and may cause loss of autoregulation. The cerebral vascular response to hypocapnia is reduced in those with the most severe injuries (subdural hematomas and diffuse contusions), and there is substantial local variability in perfusion. While the CBF level at which irreversible ischemia occurs has not been clearly established, ischemic cell change has been demonstrated in 90% of those who die following TBI, and there is PET evidence that such damage is likely to occur when CBF drops below 15-20 cc/100 g/min. A prospective randomized clinical trial has determined that outcomes are worse when TBI patients are treated with chronic prophylactic hyperventilation therapy. Within the standard, guideline, and options, specific paCO2 thresholds have been described that are different for each of the three parameters. These individual thresholds were selected based on the preponderance of literature supporting those thresholds in the contexts of the statements which included them. With the exception of the threshold included for the standard in this guideline, it is emphasized that the paCO2 threshold is not as important as the general concept of hyperventilation. The preponderance of the physiologic literature concludes that hyperventilation during the first few days following severe traumatic brain injury, whatever the threshold, is potentially deleterious in that it can promote cerebral ischemia.     

Comparison of half-molar sodium lactate and mannitol to treat brain edema in severe traumatic brain injury: A systematic review

PurposeHypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP).MethodsThis study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were “half-molar sodium lactate”, “mannitol”, “cerebral edema or brain swelling”, and “severe traumatic brain injury”. The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3.ResultsFrom 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09).ConclusionHalf-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.     

Jugular venous oxygen saturation thresholds in trauma patients may not extrapolate to ischemic stroke patients: lessons from a preliminary study

The authors' first examinations of 10 patients with severe hemispheric stroke indicate that bedside monitoring of cerebral blood flow (CBF) is of clinical value as a prognostic tool for outcome and as therapy of elevated intracranial pressure (ICP). Jugular venous oximetry, which is easier to handle and provides on-line data, may also be of prognostic value in patients with ischemic stroke. No clinical studies are available on patients with hemispheric infarctions. Therefore, in a second data analysis from the same patient population, the authors' objective was to estimate the clinical value of monitoring cerebral hemodynamics and metabolism with jugular bulb catheters in treatment of severe postischemic brain edema. In 10 patients with severe hemispheric infarctions, ICP, jugular venous oxygen saturation (SjvO2), CBF, and cerebral metabolic rate of oxygen (CMRO2) were measured prospectively. A total of 101 ICP, SjvO2, and 92 CBF measurements were obtained. Only two SjvO2 values were below the critical thresholds to detect secondary ischemic events defined in trauma patients (SjvO2 < 50%). Intracranial pressure elevations more than 20 mm Hg and pupillary disturbances were treated with osmotherapy (mannitol or hypertonic NaCl hydroxyethyl starch solution) or mild hyperventilation in combination with tromethamine-buffer. In 8 of 17 pairs of measurements with treated elevated ICP, CMRO2 varied and changes of SjvO2 did not reflect changes in CBF. Jugular bulb oximetry should interpreted with caution in patients with severe hemispheric infarction. Critical thresholds defined in trauma patients may not be extrapolated to ischemic stroke.     

Cerebral vasoreactivity and the prediction of outcome in severe traumatic brain lesions

Mean hemispheric blood flow (CBF) was studied in 38 comatose, severely brain-injured patients following intravenous administration of xenon-133. Repeated measurements were performed in order to evaluate cerebral vasoreactivity following a decrease in PaCO2. Simultaneously, arterial-venous oxygen differences (AVDO2) and intracranial pressure (ICP) were measured. An impaired CBF response to hyperventilation (delta CBF/delta PaCO2 less than 1.0) was obtained in 22 patients. Three of 16 patients with preserved CO2-reactivity died because of their brain injuries and 12 patients reached good recovery/moderate disability. In the group of patients with impaired vasoreactivity 11 of 22 patients died and only three patients reached good recovery/moderate disability. The study documents that in patients with severe traumatic brain lesions measurements of cerebral vasoreactivity to hyperventilation give prognostic information that is not obtained by clinical observations or CT-scanning.     

Cerebral oxygen consumption and ischemia in traumatic brain injury

AIM: Clinical and experimental studies have shown a reduction of cerebral blood flow (CBF) and metabolic alterations following traumatic brain injury (TBI). The incidence of ischemia and the meaning of post-traumatic metabolic alterations are still unclear. METHODS: Revision of CBF and metabolic changes following TBI based on the literature and on our clinical experience. RESULTS: Cerebral ischemia and metabolic alterations are part of the secondary insults/damage leading to an increased damage following TBI. Global ischemia occurs early following TBI as shown by CBF measurements and by greater values of arterio-jugular difference of oxygen (AJDO(2)) during the 1(st) 24 hours postinjury. Post-traumatic ischemia should be defined based on the relationships between CBF and on the metabolic requirements of the brain. Regional ischemia occurs more frequently than global ischemia as shown by regional monitoring of cerebral oxygenation. Following TBI there is a transient phase of increased glycolitic activity followed by a more prolonged phase of reduced metabolic rate of glucose (CMRglc) and oxygen (CMRO(2)). The extent of CMRO(2) reduction is a marker of injury severity and it is associated with unfavorable outcome. CONCLUSION: Cerebral ischemia occurs following TBI and should be defined based on CBF value and the metabolic needs of the brain. Global monitoring of cerebral oxygenation adequacy should be combined with regional monitoring. The meaning of high AJDO(2) values should be reconsidered: if they can highlights potential ischemia they are also showing a still living brain with a partially preserved oxygen extraction capability.     

Effects of hyperbaric oxygenation therapy on cerebral metabolism and intracranial pressure in severely brain injured patients

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment.     

Effects of hyperbaric oxygenation

OBJECT: Hyperbaric oxygenation (HBO) therapy has been shown to reduce mortality by 50% in a prospective randomized trial of severely brain injured patients conducted at the authors' institution. The purpose of the present study was to determine the effects of HBO on cerebral blood flow (CBF), cerebral metabolism, and intracranial pressure (ICP), and to determine the optimal HBO treatment paradigm. METHODS: Oxygen (100% O2, 1.5 atm absolute) was delivered to 37 patients in a hyperbaric chamber for 60 minutes every 24 hours (maximum of seven treatments/patient). Cerebral blood flow, arteriovenous oxygen difference (AVDO2), cerebral metabolic rate of oxygen (CMRO2), ventricular cerebrospinal fluid (CSF) lactate, and ICP values were obtained 1 hour before and 1 hour and 6 hours after a session in an HBO chamber. Patients were assigned to one of three categories according to whether they had reduced, normal, or raised CBF before HBO. In patients in whom CBF levels were reduced before HBO sessions, both CBF and CMRO2 levels were raised 1 hour and 6 hours after HBO (p < 0.05). In patients in whom CBF levels were normal before HBO sessions, both CBF and CMRO2 levels were increased at 1 hour (p < 0.05), but were decreased by 6 hours after HBO. Cerebral blood flow was reduced 1 hour and 6 hours after HBO (p < 0.05), but CMRO2 was unchanged in patients who had exhibited a raised CBF before an HBO session. In all patients AVDO2 remained constant both before and after HBO. Levels of CSF lactate were consistently decreased 1 hour and 6 hours after HBO, regardless of the patient's CBF category before undergoing HBO (p < 0.05). Intracranial pressure values higher than 15 mm Hg before HBO were decreased 1 hour and 6 hours after HBO (p < 0.05). The effects of each HBO treatment did not last until the next session in the hyperbaric chamber. CONCLUSIONS: The increased CMRO2 and decreased CSF lactate levels after treatment indicate that HBO may improve aerobic metabolism in severely brain injured patients. This is the first study to demonstrate a prolonged effect of HBO treatment on CBF and cerebral metabolism. On the basis of their data the authors assert that shorter, more frequent exposure to HBO may optimize treatment.     

Cerebral blood flow and metabolism during adenosine–induced hypotension in patients undergoing cerebral aneurysm surgery

The effects of adenosine-induced hypotension on cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral lactate production, together with systemic haemodynamics, were studied in 10 patients undergoing cerebral aneurysm surgery in neurolept anaesthesia with controlled hyperventilation. CBF changes were determined in six of the patients with a retrograde thermodilution technique in the jugular vein. Hypotension was induced with a continuous infusion of adenosine in the superior vena cava. The dose range was 0.06-0.35 mg/kg/min, and this caused a 42% reduction in mean arterial blood pressure (MABP) from 79 +/- 4 to 46 +/- 1 mmHg (10.5 +/- 0.5 to 6.1 +/- 0.1 kPa) through a profound reduction in systemic vascular resistance (SVR), which amounted to 61%. No significant change occurred in CBF. Whole body AV-difference of oxygen was decreased by 37%, and cerebral AV-difference by 28%, corresponding to reductions in whole body oxygen uptake and CMRO2 of 16 and 17%, respectively. Cerebral AV-difference of lactate did not change. In the posthypotensive period MABP was increased by 10%, together with a minor increase in CBF (15%). It is concluded, that adenosine-induced hypotension at MABP levels between 40-50 mmHg (5.3-6.7 kPa) does not affect cerebral oxygenation unfavourably, and may even offer a protective effect by reducing cerebral oxygen demand. The slight CBF increase in the posthypotensive period was probably secondary to an increase in MABP together with a blunted autoregulation, but in no case was this effect considered to be harmful for the patient.     

The response of the canine cerebral circulation to hyperventilation during anesthesia with desflurane

Arterial CO2 tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) and cerebral vascular resistance (CVR) in animals and humans. The normal responsiveness of the cerebral vasculature to PaCO2 is approximately 2 ml.min-1.100 g-1.mmHg-1. This study examined the effect of desflurane, a new volatile anesthetic, on the responsiveness of the cerebral vasculature to changes in PaCO2. Mean arterial pressure (MAP), CBF, CVR, intracranial pressure (ICP), and cerebral metabolic rate for O2 (CMRO2) were measured in five dogs anesthetized with desflurane (0.5-1.5 MAC) at normocapnia (PaCO2 = 40 mmHg) and at two levels of hypocapnia (PaCO2 = approximately 30 and approximately 20 mmHg). Under desflurane anesthesia, similar changes in CBF and CVR occurred with hyperventilation at all MAC levels of desflurane. At 0.5 MAC, CBF decreased significantly, from 81 +/- 6 to 40 +/- 3 ml.min-1.100 g-1 (P less than 0.05, mean +/- SE) when PaCO2 was decreased from 40 to 24 mmHg; i.e., the CBF decreased approximately 2.6 ml.min-1.100 g-1.mmHg-1. At 1.0 MAC desflurane, CBF decreased significantly, from 79 +/- 10 to 43 +/- 5 ml.min-1.100 g-1 with hyperventilation (2.0 ml.min-1.100 g-1.mmHg-1); at 1.5 MAC desflurane, CBF decreased from 65 +/- 6 to 38 +/- 2 ml.min-1.100 g-1 with hyperventilation (1.6 ml.min-1.100 g-1.mmHg-1). Despite the significant decreases in CBF with hyperventilation, there was no significant change in ICP. Dose-dependent decreases in MAP were observed with increasing concentrations of desflurane but were not significantly affected by ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of hyperventilation,blood pressure elevation,and metabolic suppression therapy in controlling intracranial pressure after head injury

OBJECT: Hyperventilation therapy, blood pressure augmentation, and metabolic suppression therapy are often used to reduce intracranial pressure (ICP) and improve cerebral perfusion pressure (CPP) in intubated head-injured patients. In this study, as part of routine vasoreactivity testing, these three therapies were assessed in their effectiveness in reducing ICP. METHODS: Thirty-three patients with a mean age of 33 +/- 13 years and a median Glasgow Coma Scale (GCS) score of 7 underwent a total of 70 vasoreactivity testing sessions from postinjury Days 0 to 13. After an initial 133Xe cerebral blood flow (CBF) assessment, transcranial Doppler ultrasonography recordings of the middle cerebral arteries were obtained to assess blood flow velocity changes resulting from transient hyperventilation (57 studies in 27 patients), phenylephrine-induced hypertension (55 studies in 26 patients), and propofol-induced metabolic suppression (43 studies in 21 patients). Changes in ICP, mean arterial blood pressure (MABP), CPP, PaCO2, and jugular venous oxygen saturation (SjvO2) were recorded. With hyperventilation therapy, patients experienced a mean decrease in PaCO2 from 35 +/- 5 to 27 +/- 5 mm Hg and in ICP from 20 +/- 11 to 13 +/- 8 mm Hg (p < 0.001). In no patient who underwent hyperventilation therapy did SjvO2 fall below 55%. With induced hypertension, MABP in patients increased by 14 +/- 5 mm Hg and ICP increased from 16 +/- 9 to 19 +/- 9 mm Hg (p = 0.001). With the aid of metabolic suppression, MABP remained stable and ICP decreased from 20 +/- 10 to 16 +/- 11 mm Hg (p < 0.001). A decrease in ICP of more than 20% below the baseline value was observed in 77.2, 5.5, and 48.8% of hyperventilation, induced-hypertension, and metabolic suppression tests, respectively (p < 0.001 for all comparisons). Predictors of an effective reduction in ICP included a high PaCO2 for hyperventilation, a high study GCS score for induced hypertension, and a high PaCO2 and a high CBF for metabolic suppression. CONCLUSIONS: Of the three modalities tested to reduce ICP, hyperventilation therapy was the most consistently effective, metabolic suppression therapy was variably effective, and induced hypertension was generally ineffective and in some instances significantly raised ICP. The results of this study suggest that hyperventilation may be used more aggressively to control ICP in head-injured patients, provided it is performed in conjunction with monitoring of SjvO2.     

Cerebral blood flow and metabolism in severely head-injured children. Part 1: Relationship with GCS score, outcome, ICP, and PVI

The literature suggests that in children with severe head injury, cerebral hyperemia is common and related to high intracranial pressure (ICP). However, there are very few data on cerebral blood flow (CBF) after severe head injury in children. This paper presents 72 measurements of cerebral blood flow ("CBF15"), using the 133Xe inhalation method, with multiple detectors over both hemispheres in 32 children aged 3 to 18 years (mean 13.6 years) with severe closed head injury (average Glasgow Coma Scale (GCS) score 5.4). In 25 of the children, these were combined with measurements of arteriojugular venous oxygen difference (AVDO2) and of cerebral metabolic rate of oxygen (CMRO2). In 30 patients, the first measurement was taken approximately 12 hours postinjury. In 18 patients, an indication of brain stiffness was obtained by withdrawal and injection of ventricular cerebrospinal fluid and calculation of the pressure-volume index (PVI) of Marmarou. The CBF and CMRO2 data were correlated with the GCS score, outcome, ICP, and PVI. Early after injury, CBF tended to be lower with lower GCS scores, but this was not statistically significant. This trend was reversed 24 hours postinjury, as significantly more hyperemic values were recorded the lower the GCS score, with the exception of the most severely injured patients (GCS score 3). In contrast, mean CMRO2 correlated positively with the GCS score and outcome throughout the course, but large standard deviations preclude making predictions based on CMRO2 measurements in individual patients. Early after injury, there was mild uncoupling between CBF and CMRO2 (CBF above metabolic demands, low AVDO2) and, after 24 hours, flow and metabolism were completely uncoupled with an extremely low AVDO2. Consistently reduced flow as found in only four patients; 28 patients (88%) showed hyperemia at some point in their course. This very high percentage of patients with hyperemia, combined with the lowest values of AVDO2 found in the literature, indicates that hyperemia or luxury perfusion is more prevalent in this group of patients. The three patients with consistently the highest CBF had consistently the lowest PVI: thus, the patients with the most severe hyperemia also had the stiffest brains. Nevertheless, and in contrast to previous reports, no correlation could be established between the course of ICP or PVI and the occurrence of hyperemia, nor was there a correlation between the levels of CBF and ICP at the time of the measurements. The authors argue that this lack of correlation is due to: 1) a definition of hyperemia that is too generous, and 2) the lack of a systematic relationship between CBF and cerebral blood volume