Effect of cerebral perfusion pressure on contusion volume following impact injury

OBJECT: Although it is generally acknowledged that a sufficient cerebral perfusion pressure (CPP) is necessary for treatment of severe head injury, the optimum CPP is still a subject of debate. The purpose of this study was to investigate the effect of various levels of blood pressure and, thereby, CPP on posttraumatic contusion volume. METHODS: The left hemispheres of 60 rats were subjected to controlled cortical impact injury (CCII). In one group of animals the mean arterial blood pressure (MABP) was lowered for 30 minutes to 80, 70, 60, 50, or 40 mm Hg 4 hours after contusion by using hypobaric hypotension. In another group of animals the MABP was elevated for 3 hours to 120 or 140 mm Hg 4 hours after contusion by administering dopamine. The MABP was not changed in respective control groups. Intracranial pressure (ICP) was monitored with an ICP microsensor. The rats were killed 28 hours after trauma occurred and contusion volume was assessed using hematoxylin and eosin-stained coronal slices. No significant change in contusion volume was caused by a decrease in MABP from 94 to 80 mm Hg (ICP 12+/-1 mm Hg), but a reduction of MABP to 70 mm Hg (ICP 9+/-1 mm Hg) significantly increased the contusion volume (p < 0.05). A further reduction of MABP led to an even more enlarged contusion volume. Although an elevation of MABP to 120 mm Hg (ICP 16+/-2 mm Hg) did not significantly affect contusion volume, there was a significant increase in the contusion volume at 140 mm Hg MABP (p < 0.05; ICP 18+/-1 mm Hg). CONCLUSION: Under these experimental conditions, CPP should be kept within 70 to 105 mm Hg to minimize posttraumatic contusion volume. A CPP of 60 mm Hg and lower as well as a CPP of 120 mm Hg and higher should be considered detrimental.     

Small volume resuscitation with HyperHaes improves pericontusional perfusion and reduces lesion volume following controlled cortical impact injury in rats

The hyperosmolar and hyperoncotic properties of HyperHaes (HHES) might improve impaired posttraumatic cerebral perfusion. Possible beneficial effects on pericontusional perfusion, brain edema, and contusion volume were investigated in rats subjected to controlled cortical impact (CCI). Male Sprague-Dawley rats (n = 60) anesthetized with isoflurane were subjected to a left temporoparietal CCI. Thereafter, rats were randomized to receive HHES (10% hydroxyethylstarch, 7.5% NaCl) or physiological saline solution (4 mL/kg body weight) intravenously. Mean arterial blood pressure (MABP) and intracranial pressure (ICP) were determined before and following CCI, after drug administration and 24 h later. Regional pericontusional cortical perfusion was determined by scanning laser Doppler flowmetry before CCI, and 30 min, 4 and 24 h after injury. At 24 h brain swelling and water content were measured gravimetrically. At 7 days, cortical contusion volume was determined planimetrically. MABP was not influenced by HHES. ICP was significantly decreased immediately after HHES infusion (5.7 +/- 0.4 vs. 7.1 +/- 1.0 mm Hg; p < 0.05). Pericontusional cortical perfusion was significantly decreased by 44% compared to pre-injury levels (p < 0.05). HHES significantly improved cortical perfusion at 4 h after CCI, approaching baseline values (85 +/- 12%). While increased posttraumatic brain edema was not reduced by HHES at 24 h, cortical contusion volume was significantly decreased in the HHES-treated rats at 7 days after CCI (23.4 +/- 3.5 vs. 39.6 +/- 6.2 mm3; p < 0.05). Intravaneous administration of HHES within 15 min after CCI has a neuroprotective potential, as it significantly attenuated impaired pericontusional perfusion and markedly reduced the extent of induced structural damage.     

Effect of early and delayed decompressive craniectomy on secondary brain damage after controlled cortical impact in mice

The timing of decompressive craniectomy for the treatment of increased intracranial pressure (ICP) after traumatic brain injury (TBI) is a widely discussed clinical issue. Although we showed recently that early decompression is beneficial following experimental TBI, it remains unclear to what degree decompression craniectomy reduces secondary brain damage and if craniectomy is still beneficial when it is delayed by several hours as often inevitable during daily clinical practice. The aim of the current study was therefore to investigate the influence of craniectomy on secondary contusion expansion and brain edema formation and to determine the therapeutic window of craniectomy. Male C57/Bl6 mice were subjected to controlled cortical impact injury. Contusion volume, brain edema formation, and opening of the blood-brain barrier were investigated 2, 6, 12, and 24 h and 7 days after trauma. The effect of decompression craniectomy on secondary brain damage was studied in control mice (closed skull) and in animals craniotomized immediately or with a delay of 1, 3, or 8 h after trauma. Twenty-four hours after trauma, the time point of maximal lesion expansion (+60% vs. 15 min after trauma) and brain edema formation (+3.0% water content vs. sham), contusion volume in craniotomized mice did not show any secondary expansion; that is, contusion volume was similar to that observed in mice sacrificed immediately after trauma (18.3 +/- 5.3 vs. 22.2 +/- 1.4 mm(3)). Furthermore, brain edema formation was reduced by 52% in craniotomized animals. The beneficial effect of craniectomy was still present even when treatment was delayed by up to 3 h after trauma (p < 0.05). The current study clearly demonstrates that early craniectomy prevents secondary brain damage and significantly reduces brain edema formation after experimental TBI. Evaluation of early craniectomy as a therapeutic option after TBI in humans may therefore be indicated.     

Intracranial pressure changes following traumatic brain injury in rats: lack of significant change in the absence of mass lesions or hypoxia

Traumatic brain injury (TBI) often causes raised intracranial pressure (ICP), with >50% of all TBI- related deaths being associated with this increase in ICP. To date, there is no effective pharmacological treatment for TBI, partly because widely used animal models of TBI may not replicate many of the pathophysiological responses observed in humans, and particularly the ICP response. Generally, rodents are the animal of choice in neurotrauma research, and edema formation has been demonstrated in rat models; however, few studies in rats have specifically explored the effects of TBI on ICP. The aim of the current study was to investigate the ICP response of rats in two different, focal and diffuse, injury models of TBI. Adult male Sprague-Dawley rats were subjected to brain trauma by either lateral fluid percussion or impact-acceleration induced injury, in the presence or absence of secondary hypoxia. ICP, mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were monitored for 4?h after TBI. TBI alone or coupled with hypoxia did not result in any significant increase of ICP in rats unless there was an intracranial hemorrhage. At all other times, changes in CPP were the result of changes in MABP and not ICP. Our results suggest that rats may be able to compensate for the intracranial expansion associated with cerebral edema after TBI, and that they only develop a consistent post-traumatic increase in ICP in the presence of a mass lesion. Therefore, they are an inappropriate model for the investigation of ICP changes after TBI, and for the development of therapies targeting ICP.     

Propofol versus isoflurane anesthesia under hypothermic conditions: effects on intracranial pressure and local cerebral blood flow after diffuse traumatic brain injury in the rat

BACKGROUND: The aim of this study was to compare the cerebral protective effects of two known protective anesthetics, isoflurane and propofol, when these were used in combination with moderate hypothermia (33-34 degrees C) after diffuse traumatic brain injury (TBI) in the rat. We assessed cerebral protection by measuring local cerebral blood flow (LCBF), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and intracranial pressure (ICP). METHODS: Sixteen female Wistar rats weighing 275 to 350 g were anesthetized and subjected to an accelerated-impact weight-drop model of diffuse TBI. Hypothermia (33-34 degrees C) was induced 45 minutes after TBI (baseline), and was maintained for 180 minutes. The isoflurane group (n = 8) received 70% N(2)O in O(2), and isoflurane at 0.9 +/- 0.04%. The propofol group (n = 8) received 70% N(2)O in O(2) and a propofol infusion (12 mg/kg/hr). LCBF was measured by laser Doppler flowmeter. MABP, ICP, and brain and rectal temperatures were measured every 15 minutes from baseline through 180 minutes. Blood gas and hematocrit testing was also done at baseline and every 60 minutes thereafter to assess the animals' physiological state. RESULTS: In the isoflurane group, MABP and CPP decreased significantly from baseline to 180 minutes (p < 0.05 and p < 0.01, respectively), and MABP was significantly lower than the pressure in the propofol group from 45 minutes through 180 minutes (p < 0.05, p < 0.01). ICP and LCBF remained unchanged in this group. In the propofol group, from baseline to 180 minutes, CPP increased to maximum 120 +/- 8 mmHg at 75 minutes from 98 +/- 5 mmHg (p < 0.05) and ICP fell from 18 +/- 2 mmHg to 7 +/- 1 mmHg (p < 0.01); and the latter was significantly lower than ICP in the isoflurane group (p < 0.05, p < 0.01, p < 0.001). LCBF in this group was significantly higher than LCBF in the isoflurane group in the last 30 minutes of the experiment (p < 0.05). The propofol group showed no change in MABP over the course of the experiment. CONCLUSION: In the clinical setting, propofol anesthesia may be better for use in combination with hypothermia in cases of traumatic brain injury, as it reduces ICP and increases CPP under these conditions.     

Relationship of cerebral perfusion pressure and survival in pediatric brain-injured patients

BACKGROUND: Adult brain injury studies recommend maintaining cerebral perfusion pressure (CPP) above 70 mm Hg. We evaluated CPP and outcome in brain-injured children. METHODS: We retrospectively reviewed the hospital courses of children at two Level I trauma centers who required insertion of intracranial pressure (ICP) monitors for management of traumatic brain injury. ICP, CPP, and mean arterial pressure were evaluated hourly, and means were calculated for the first 48 hours after injury. RESULTS: Of 188 brain-injured children, 118 had ICP monitors placed within 24 hours of injury. They suffered severe brain injury, with average admitting Glasgow Coma Scale scores of 6 +/- 3. Overall mortality rate was 28%. No patient with mean CPP less than 40 mm Hg survived. Among patients with mean CPP in deciles of 40 to 49, 50 to 59, 60 to 69, or 70 mm Hg, no significant difference in Glasgow Outcome Scale distribution existed. CONCLUSION: Low mean CPP was lethal. In children with survivable brain injury (mean CPP > 40 mm Hg), CPP did not stratify patients for risk of adverse outcome.     

Ubiquitin reduces contusion volume after controlled cortical impact injury in rats

Recent data suggest that ubiquitin has anti-inflammatory properties and therapeutic potential after severe trauma and brain injuries. However, direct evidence for its neuroprotective effects has not yet been provided. We hypothesized that ubiquitin treatment is neuroprotective, and thus reduces brain edema formation and cortical contusion volume after closed traumatic brain injuries. To test this hypothesis, a focal cortical contusion was induced using a controlled cortical impact (CCI) model in Sprague-Dawley rats. Animals (n = 27) were randomized to either 1.5 mg/kg ubiquitin or vehicle (placebo) intravenously within 5 min after CCI. Blood pressure, arterial blood gases (ABG) and intracranial pressure (ICP) were monitored. Ubiquitin serum and cerebrospinal fluid levels were measured by ELISA. Brain water content was quantified gravimetrically after 24 h and cerebral contusion volume was determined in triphenyltetrazolium-chloride stained brains after 7 days. All animals recovered to normal activity. ICP and cerebral perfusion pressures were normal at the end of the observation period. Ubiquitin serum and CSF levels at 24 h and 7 days after CCI were similar in both groups. With ubiquitin brain water content of the injured hemisphere was slightly lower (n = 6/group; 79.97 +/- 0.29% vs. 81.11 +/- 0.52%; p = 0.08). Cortical contusion volume was significantly lower with ubiquitin (n = 7-8/group; 32.88 +/- 2.1 mm(3) vs. 43.96 +/- 4.56 mm(3); p = 0.025). This study shows that ubiquitin treatment after brain injury has direct neuroprotective effects, as demonstrated by improved brain morphology 7 days after brain injury. In connection with its beneficial effects in our previous studies, these data suggest ubiquitin as a promising candidate protein therapeutic for the treatment of brain injuries.     

Neuroprotective Effect of Melatonin on Cortical Impact Injury in the Rat

Summary  The pineal hormone melatonin is a highly efficient physiological scavenger of free radicals involved in secondary brain damage. A variety of experimental studies have demonstrated a neuroprotective effect for melatonin, based on its antioxidant activity. The purpose of the present study was to investigate the time-dependency and a possible protective effect of exogenous melatonin in the cortical impact model in rats. The protective effect was quantified determining contusion volume, brain edema and brain water content.  45 anesthetized male Sprague-Dawley rats (250–350 mg) were subjected to cortical impact injury of moderate severity (7 m/s, deformation 2 mm). Melatonin (100 mg/kg bw i.p.), or a vehicle was injected 20 min before trauma, immediately after, and 1 and 2 hours after trauma during daytime and nighttime. Posttraumatic lesion volume using hematoxylin-eosin staining, hemispheric swelling, brain water content, cerebral perfusion pressure and intracranial pressure 24 hours after injury were investigated.  Melatonin, given during nighttime, significantly reduced contusion volume corresponding to a mean reduction of contusion volume of 27% (placebo, n=7: 41.9±5.2 mm³, melatonin, n=8: 30.5±4.2 mm³, p<0.05). Given during daytime, the reduction in contusion volume was not significant (placebo, n=8: 42.1±5.1 mm³, melatonin, n=8: 35.9±2.2 mm³, reduction of 15%, p=0.08, n.s.). Hemispheric swelling was unchanged by melatonin treatment. Mean arterial blood pressure and rectal temperature remained stable before and after the cortical impact injury and injection of melatonin. This study shows that melatonin significantly reduces contusion volume with major effects during night.     

Effect of decompression craniotomy on increase of contusion volume and functional outcome after controlled cortical impact in mice

If, how, and when decompressive craniotomy should be used for the treatment of increased intracranial pressure after traumatic brain injury are widely discussed clinical subjects. Despite the large number of clinical studies addressing this issue, experimental evidence of a beneficial or detrimental role of decompressive craniotomy after brain trauma is sparse. Therefore, we investigated the influence of craniotomy on intracranial pressure, contusion volume, and functional outcome in a model of traumatic brain injury in mice. Male C57/Bl6 mice were craniotomized above the right parietal cortex and were subjected to controlled cortical impact injury. In control mice, the craniotomy was closed immediately after trauma, whereas in treated animals the craniotomy was left open. In control mice intracranial pressure (ICP) increased to a maximum of 23.7 +/- 3.1 mm Hg 6 h after trauma (p < 0.001), while in craniotomized animals, no ICP increase was observed. Twenty-four hours after trauma, the point in time of maximal lesion expansion, contusion volume in craniotomized mice was 40% smaller as compared to controls (18.3 +/- 2.0 vs. 30.2 +/- 3.5 mm(3), p < 0.04). Furthermore, craniotomized mice showed significantly improved motor function in a beam walking task (p < 0.04) and faster recovery of body weight after trauma (p < 0.02). Our results demonstrate that craniotomy blunts post-traumatic ICP increase, significantly reduces secondary brain damage and improves functional outcome after experimental TBI. Careful clinical evaluation of craniotomy as a therapeutic option after TBI in man may therefore be indicated.     

Influence of norepinephrine and dopamine on cortical perfusion,EEG activity,extracellular glutamate,and brain edema in rats after controlled cortical impact injury

Following traumatic brain injury, catecholamines given to ameliorate cerebral perfusion may induce brain damage via cerebral arteriolar constriction and increased neuronal excitation. In the present study the acute effects of norepinephrine and dopamine on pericontusional cortical perfusion (rCBF), electroencephalographic (EEG) activity, extracellular glutamate, and brain edema were investigated in rats following controlled cortical impact injury (CCI). rCBF, cerebral perfusion pressure (CPP), EEG activity, and glutamate were determined before, during, and after infusing norepinephrine or dopamine, increasing MABP to 120 mm Hg for 90 min at 4 h after CCI. Control rats received physiological saline. At 8 h after CCI, hemispheric swelling and water content were determined gravimetrically. Following CCI, rCBF was significantly decreased. In parallel to elevating MABP and CPP, rCBF was significantly increased by norepinephrine and dopamine, being mostly pronounced with norepinephrine (+44% vs. +29%). In controls, rCBF remained diminished (-45%). EEG activity was significantly increased by norepinephrine and dopamine, while pericontusional glutamate was only elevated by norepinephrine (28 +/- 6 vs. 8 +/- 4 microM). Brain edema was not increased compared to control rats. Despite significantly increasing MABP and CPP to the same extent, norepinephrine and dopamine seem to differentially influence pericontusional cortical perfusion and glutamatergic transmission. In addition to the pressure-passive increase in CPP local cerebral effects seem to account for the sustained norepinephrine-induced increase in pericontusional cortical perfusion. The significantly elevated pericontusional glutamate concentrations in conjunction with the increased EEG activity suggest a sustained metabolically driven increase in cortical perfusion during norepinephrine infusion.     

Increase in the chronically monitored cerebrospinal fluid pressure after experimental brain injury in rats

The early effects of experimental brain injury with diffuse axonal lesions on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) in rats have been already studied. The aim of this experiment was to examine the effects of brain injury on ICP, MAP and CPP during the first few days post-injury. In order to do that, an accurate technique of ICP measurement had to be developed. In a series of eight rats, a translumbar intrathecal catheter (TIC) was surgically introduced allowing repeated measurements of cerebrospinal fluid pressure (CSFP). Under anaesthesia, a second series of nine rats were equipped simultaneously with TIC and an intracranial fiberoptic device to measure ICP. Simultaneous measurements of CSFP and ICP were recorded for baseline values, than during and after jugular compression which was intended to induce an acute and significant increase in ICP. A third series of 53 rats having TIC received an experimental severe brain injury. MAP was measured non-invasively and CPP was calculated as CPP MAP. CSFP, MAP and CPP were intermittently measured during 5-6 post-traumatic days and compared to the values obtained during ten control rats (SHAM). A clinical score was used to compare clinical condition. The results showed that the translumbar CSFP accurately measured ICP in rats having normal or acutely increased ICP. The experimental brain injury induced increased CSFP lasting up to 5-6 days, with increased MAP during the first 6hours. CPP values were compromised at 24-48hours. The clinical performance was reduced in the brain injured rats. The translumbar technique of CSFP measurement reflected exact ICP in normal and acutely increased ICP in rats. Experimental brain injury with diffuse axonal lesions can increase lumbar CSFP in rats for many days.     

Differential concentration-dependent effects of prolonged norepinephrine infusion on intraparenchymal hemorrhage and cortical contusion in brain-injured rats

Under clinical conditions catecholamines are infused to elevate cerebral perfusion pressure and improve impaired posttraumatic cerebral microcirculation. This, however, is associated with the risk of additional hemorrhage in the acute phase following traumatic brain injury. In the present study we investigated the dose-dependent effects of prolonged norepinephrine infusion on arterial blood pressure, blood glucose, and structural damage in brain-injured rats. At 4 h following induction of a focal cortical contusion (CCI), 40 rats were randomized to receive low (0.15), medium (0.3), or high dose (1 microg/kg/min) norepinephrine. Control rats were given equal volume of NaCl. Norepinephrine and NaCl were infused intravenously via Alzet osmotic pumps for 44 h. Mean arterial blood pressure (MABP), blood gases and blood glucose were determined before, at 4, 24, 48 h after CCI in repeatedly anesthetized rats (n = 28). Systolic arterial blood pressure (SABP) was measured using the tail cuff method in awake, restrained rats (n = 12). Cortical contusion and intraparenchymal hemorrhage volume were quantified at 48 h in all rats. MABP determined in anesthetized rats was only marginally increased. SABP was significantly elevated during infusion of medium and high dose norepinephrine in awake rats, exceeding 140 mm Hg. Medium and high dose norepinephrine significantly increased cortical hemorrhage by 157% and 142%, without increasing the cortical contusion volume. Low dose norepinephrine significantly reduced the cortical contusion by 44%. Norepinephrine aggravates the underlying brain damage during the acute posttraumatic phase. Future studies are needed to determine the least deleterious norepinephrine concentration.     

Riluzole reduces brain swelling and contusion volume in rats following controlled cortical impact injury

Modulation of the glutamatergic and excitotoxic pathway may attenuate secondary damage following traumatic brain injury by reducing presynaptic glutamate release and blocking sodium channels in their inactivated state. The aim of the present study was to investigate the neuroprotective potential of riluzole in traumatic brain-injured rats. A left temporoparietal contusion was induced in 70 male Sprague-Dawley rats (controlled cortical impact injury). Riluzole (8 mg/kg body weight) was given 30 min, and 6, 24, and 30 h after trauma, while control rats received physiological saline. Experiments were performed at two different degrees of trauma severity as defined by penetration depth of the impactor rod (1 vs. 1.5 mm) with the aim of investigating impact of severity of tissue damage on the neuroprotective potential of riluzole. At 48 h after trauma, brains were removed to determine hemispheric swelling and water content and to assess cortical contusion volume. Before brain removal cisternal cerebrospinal fluid (CSF) was collected in all rats to determine the effects of riluzole on substances associated with edema formation. For this, the excitatory transmitter glutamate, the volume-regulatory amino acid taurine, and the ATP-degradation product hypoxanthine were analyzed by high-performance liquid chromatography. Overall, the degree of tissue damage seems to influence the neuroprotective potential of riluzole. In rats with a less severe trauma (1-mm penetration depth), hemispheric swelling, cerebral water content of the traumatized hemisphere and cortical contusion volume were significantly reduced under riluzole compared to controls (p < 0.05). In rats with a more severe trauma (1.5-mm penetration depth), the neuroprotective effect of riluzole failed to reach statistical significance. Following trauma, CSF glutamate, taurine, and hypoxanthine levels were significantly increased compared to nontraumatized rats (p < 0.001). However, these neurochemical parameters as measured in cisternal CSF failed to reflect trauma-dependent increases in severity of tissue damage and did not reveal riluzole-mediated neuroprotection. Under the present study design, riluzole significantly reduced brain edema formation and contusion volume in rats subjected to a mild focal cortical contusion.     

Effect of naloxone on experimental head injury in cats

Forty-five cats were randomly divided into four groups: (1) the control group (n = 11); (2) the head injury group (n = 17); (3) the naloxone group (n = 8); (4) the saline group (n = 9). Naloxone (10mg/kg) was directly injected into cisterna cerebello-medullaris 2 hours after injury. The results showed that naloxone had some effects in maintaining MABP, CPP, lowering of ICP and edema of brain).     

Prone position in mechanically ventilated patients with reduced intracranial compliance

BACKGROUND: Prone position has been used for several years to treat acute lung insufficiency, but in previous studies patients with unstable intracranial pressure (ICP) are mostly excluded. The aim of this study was to investigate if prone position is a safe and useful treatment in patients with reduced intracranial compliance. METHODS: A consecutive, prospective pilot study of 11 patients admitted to the neuro intensive care unit (NICU) due to traumatic brain injury or intracerebral haemorrhage. ICP, cerebral perfusion pressure (CPP), heart rate (HR), mean arterial blood pressure (MABP), arterial partial pressure of oxygen (PaO(2)), arterial partial pressure of carbon dioxide (PaCO(2)), arterial oxygen saturation (SaO(2)) and respiratory system compliance were measured before, three times during and two times after the patients were placed in the prone position. RESULTS: No significant changes were demonstrated in ICP, CPP or MABP. PaO(2) and SaO(2) were significantly increased in the prone position. HR was significantly increased in the prone position and after 10 min in the supine post-prone position and the respiratory system compliance was increased after 1 h in the supine post-prone position. CONCLUSION: Turning NICU patients from the supine to the prone position did not influence ICP, CPP or MABP, but significantly improved patient PaO(2), SaO(2) and respiratory system compliance.     

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage

OBJECT: Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. METHODS: Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. CONCLUSIONS: Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.     

Effects of nifedipine on intracranial pressure in neurosurgical patients with arterial hypertension

The effects of nifedipine, 20 mg administered via a nasogastric tube, on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were examined. Nifedipine was administered to treat arterial hypertension (greater than 180 mm Hg, systolic). Ten measurements were made in eight patients with cerebrovascular disease or head trauma. The mean arterial blood pressure (MABP) and ICP were measured before and for 30 minutes after the administration of nifedipine. The MABP gradually decreased and reached its lowest value at approximately 10 minutes after initiation of nifedipine administration, and thereafter remained unchanged. The MABP decreased significantly from 128 +/- 8 (mean +/- standard deviation) to 109 +/- 7 mm Hg, and the CPP decreased from 105 +/- 11 to 84 +/- 10 mm Hg. The ICP increased by 1 to 10 mm Hg in eight of 10 measurements, and the mean change of ICP from 19 +/- 7 to 22 +/- 6 mm Hg was statistically significant. These changes were not accompanied by alterations in neurological signs. The results suggest that enteral nifedipine produces a small but statistically significant increase in ICP. Accordingly, neurological signs must be closely observed to detect deterioration, which can be caused by an increase in ICP and/or a decrease in CPP.     

Focal brain injury results in severe cerebral ischemia despite maintenance of cerebral perfusion pressure.

Severe head injury often causes an increase in intracranial pressure (ICP) and decreases in cerebral blood flow (CBF) and cerebral oxygen delivery (CO2del). To determine if this reduction in CBF and CO2del would produce cerebral ischemia and if this reduction would be abrogated by maintaining global cerebral perfusion pressure (CPP), we studied CPP, ICP, CBF, CO2del, cerebral oxygen extraction ratio (CO2ER), and cortical water content (CWC) in a porcine model of focal cryogenic brain injury. Fifteen mature swine were randomized to two groups. The experimental group (n = 7) had a brain lesion and was studied for 24 hours. The control group (n = 8) was instrumented only. Cryogenic injury significantly increased ICP and decreased CBF and CO2del compared with controls. There were no significant differences in CPP between the groups for the entire experiment, and the CPP was well above the ischemic threshold. The CO2ER significantly increased in the first three hours after brain injury. However, CO2ER in experimental animals tended to decrease 12 hours after brain injury and was not significantly different from that in controls. Cryogenic injury significantly increased the CWC in the lesioned hemisphere. These data indicate that focal brain injury results in persistent ischemia despite the normalization of CPP, suggesting that a significant increase in cerebral vascular resistance (CVR) occurs after brain injury. We conclude that in addition to maintenance of CPP, intervention to reduce CVR may be important in the management of brain injury.     

Contrasting effects of dopamine therapy in experimental brain injury.

Management of cerebral perfusion pressure (CPP) is thought to be important for the treatment of traumatic brain injury (TBI). Vasopressors have been advocated as a method of increasing mean arterial blood pressure (mABP) and cerebral perfusion pressure (CPP) in the face of rising intracranial pressure (ICP). There are unresolved issues and theoretical risks about this therapy. This study therefore examined the effects of dopamine on physiological and MRI/MRS parameters in (1) a rodent model of rapidly rising intracranial pressure, caused by diffuse injury with secondary insult and (2) a model of cortical contusion. Dopamine was capable of restoring CPP in the model of rapidly rising ICP. This CPP restoration was associated with a partial restoration of CBF. Two profiles of change in the Apparent Diffusion Coefficient of water (ADCw) were seen; one in which ADCw recovered to baseline, and one in which ADCw remained persistently low. Dopamine did not alter these profiles. MRI assessed tissue water content was increased four hours after injury and dopamine increased cerebral water content in both subgroups of injury; significantly in the group with a persistently low ADCw (p < 0.01). In contusional injury, dopamine significantly worsened edema in both the ipsi- and contralateral hippocampus and temporal cortex. This occurred in the absence of ADCw changes, except in the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. In conclusion, although dopamine is capable of partially restoring CBF after injury, situations exist in which dopamine therapy worsens the swelling process. It is possible therefore that subgroups of patients exist who experience adverse effects of vasopressor treatment, and consequently the effects of vasopressor therapy in the clinical setting need to be more carefully evaluated.