Early results using cerebral perfusion pressure (CPP) management techniques in persons with traumatic brain injury indicate that treatment directed at CPP is superior to traditional techniques focused on intracranial pressure (ICP) management. The authors have continued to refine management techniques directed at CPP maintenance. One hundred fifty-eight patients with Glasgow Coma Scale (GCS) scores of 7 or lower were managed using vascular volume expansion, cerebrospinal fluid drainage via ventriculostomy, systemic vasopressors (phenylephrine or norepinephrine), and mannitol to maintain a minimum CPP of at least 70 mm Hg. Detailed outcomes and follow-up data bases were maintained. Barbiturates, hyperventilation, and hypothermia were not used. Cerebral perfusion pressure averaged 83 +/- 14 mm Hg; ICP averaged 27 +/- 12 mm Hg; and mean systemic arterial blood pressure averaged 109 +/- 14 mm Hg. Cerebrospinal fluid drainage averaged 100 +/- 98 cc per day. Intake (6040 +/- 4150 cc per day) was carefully titrated to output (5460 +/- 4000 cc per day); mannitol averaged 188 +/- 247 g per day. Approximately 40% of these patients required vasopressor support. Patients requiring vasopressor support had lower GCS scores than those not requiring vasopressors (4.7 +/- 1.3 vs. 5.4 +/- 1.2, respectively). Patients with vasopressor support required larger amounts of mannitol, and their admission ICP was 28.7 +/- 20.7 versus 17.5 +/- 8.6 mm Hg for the nonvasopressor group. Although the death rate in the former group was higher, the outcome quality of the survivors was the same (Glasgow Outcome Scale scores 4.3 +/- 0.9 vs. 4.5 +/- 0.7). Surgical mass lesion patients had outcomes equal to those of the closed head-injury group. Mortality ranged from 52% of patients with a GCS score of 3 to 12% of those with a GCS score of 7; overall mortality was 29% across GCS categories. Favorable outcomes ranged from 35% of patients with a GCS score of 3 to 75% of those with a GCS score of 7. Only 2% of the patients in the series remained vegatative and if patients survived, the likelihood of their having a favorable recovery was approximately 80%. These results are significantly better than other reported series across GCS categories in comparisons of death rates, survival versus dead or vegetative, or favorable versus nonfavorable outcome classifications (Mantel-Haenszel chi 2, p < 0.001). Better management could have improved outcome in as many as 35% to 50% of the deaths.

Cerebral perfusion pressure: management protocol and clinical results

✓ Cerebral blood flow (CBF) measurements were made in 75 adult patients with closed head injuries (mean Glasgow Coma Scale score 6.2), using the xenon-133 intravenous injection method with eight detectors over each hemisphere. All patients were studied acutely within 96 hours of trauma, and repeatedly observed until death or recovery (total of 361 examinations). Arteriojugular venous oxygen differences (AVDO2) were obtained in 55 of the patients, which permitted assessment of the balance between metabolism and blood flow, and provided estimates of cerebral metabolic rate for oxygen (CMRO2). Based on mean regional CBF, the patients were classified into two groups: those who exhibited hyperemia on one or more examinations, and those who had a consistently reduced flow during their acute illness. “Hyperemia” was defined as a normal or supernormal CBF in the presence of coma, a definition that was independently confirmed by narrow AVDO2's indicative of “luxury perfusion.” During coma, all patients showed a si...

Cerebral blood flow and metabolism in comatose patients with acute head injury: Relationship to intracranial hypertension

✓ The distribution of compliance and outflow resistance between cerebral and spinal compartments was measured in anesthetized, ventilated cats by analysis of the cerebrospinal fluid (CSF) pressure response to changes in CSF volume. Cerebral and spinal compartments were isolated by inflating a balloon positioned epidurally at the level of C-6. The change of CSF volume per unit change in pressure (compliance) and change of CSF volume per unit of time (absorption) were evaluated by inserting pressure data from the experimental responses into a series of equations developed from a mathematical model. It was found that 68% of total compliance is contributed by the cerebral compartment while the remaining 32% is contained within the spinal axis. The cerebral compartment accounted for 84% of total CSF absorption. The mechanism for spinal absorption appears to be similar in that no differences were obvious on the basis of pressure dynamics.

Compartmental analysis of compliance and outflow resistance of the cerebrospinal fluid system

Intracranial pressure (ICP) is derived from cerebral blood and cerebrospinal fluid (CSF) circulatory dynamics and can be affected in the course of many diseases of the central nervous system. Monitoring of ICP requires an invasive transducer, although some attempts have been made to measure it non-invasively. Because of its dynamic nature, instant CSF pressure measurement using the height of a fluid column via lumbar puncture may be misleading. An averaging over 30 minutes should be the minimum, with a period of overnight monitoring in conscious patients providing the optimal standard. Computer-aided recording with online waveform analysis of ICP is very helpful. Although there is no “Class I” evidence, ICP monitoring is useful, if not essential, in head injury, poor grade subarachnoid haemorrhage, stroke, intracerebral haematoma, meningitis, acute liver failure, hydrocephalus, benign intracranial hypertension, craniosynostosis etc. Information which can be derived from ICP and its waveforms includes cerebral perfusion pressure (CPP), regulation of cerebral blood flow and volume, CSF absorption capacity, brain compensatory reserve, and content of vasogenic events. Some of these parameters allow prediction of prognosis of survival following head injury and optimisation of “CPP-guided therapy”. In hydrocephalus CSF dynamic tests aid diagnosis and subsequent monitoring of shunt function.

https://jnnp.bmj.com/content/jnnp/75/6/813.full.pdf

Monitoring and interpretation of intracranial pressure

Intracerebral hemorrhage (ICH) is a devastating clinical event without effective therapies. Increasing evidence suggests that inflammatory mechanisms are involved in the progression of ICH-induced brain injury. Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including prostaglandins, chemokines, cytokines, extracellular proteases, and reactive oxygen species. Better understanding of the role of the ICH-induced inflammatory response and its potential for modulation might have profound implications for patient treatment. In this review, a summary of the available literature on the inflammatory responses after ICH is presented along with discussion of some of the emerging opportunities for potential therapeutic strategies. In the near future, additional strategies that target inflammation could offer exciting new promise in the therapeutic approach to ICH.

https://journals.sagepub.com/doi/pdf/10.1038/sj.jcbfm.9600403

Inflammation after Intracerebral Hemorrhage

The cerebrospinal fluid pressure-volume curve was determined by measuring the pressure response to rapid injection of fluid into the cisterna magna of dogs, by means of a constant flow infusion pump. The shape of the curve is complex, with two plateaus at the levels of the venous and arterial pressures, respectively. The slope dP/dV is referred to as the elastance of the system (mmHg/ml). The elastance has a low value in the normal pressure range and shifts at a fluid pressure of about 15 mmHg to a value approximately 20 times higher, with a relatively minute change in the volume of the system.

The pressure-volume curve of the cerebrospinal fluid space in dogs

A quantitative analysis of the contributions of the cranial and spinal compartments to the cerebrospinal fluid pressure-volume curve was made using dogs. The curve was determined by rapid continuous injection of fluid into the cisterna magna with simultaneous measurement of the pressure. Spinal block at the C 1 level was produced by inflation of an epidural rubber balloon allowing the recording of the pressure-volume curve for the isolated cranial system. By subtraction of the two curves obtained, the spinal pressure-volume curve could be calculated. 70 % of the variation in volume within the system was related to the spinal section and 30 % to the cranial section. The intracranial curve represents the effects on the fluid pressure of forced alterations in the volume of the intracranial vascular bed. The spinal compartment has a quantitatively defined and probably mechanically important function as an expansion vessel for the intracranial system.

Cranial and spinal components of the cerebrospinal fluid pressure‐volume curve

Effects of short-term variations in cerebrospinal fluid pressure on cerebral blood flow in dogs were measured with the radioactive krypton clearance technique of Lassen et al. The cerebrospinal fluid pressure was increased stepwise by infusion of artificial cerohrospinal fluid, the pressure range from -15 to +150 mm Hg being investigated. The cerebral blood flow remained virtually stable, when the induced cerebrospinal pressure was lower than about 100 mm Hg. At higher values the cerebral blood flow began to fall. Thus, the existence of flow auto-regulation was demonstrated also for the situation when perfusion pressure is reduced by a rise of the intracranial pressure. At very high cerebrospinal fluid pressures an additional reaction appeared in the form of a rise in the systemic arterial blood pressure. A discussion of the relative roles of these two regulating mechanisms is given.

Effects of varied cerebrospinal fluid pressure on cerebral blood flow in dogs.

In 23 dogs the cerebral blood flow was measured with the intra-arterial radioactive injection technique during and after the application of a high cerebrospinal fluid pressure by infusion of artificial cerebrospinal fluid into the subarachnoid space. Increased cerebral blood flow was observed in most cases when the cerebral perfusion pressure was restored after a period with cerebrospinal fluid pressure over 50 mm Hg. The hyperemia always occurred if during the period of high intracranial pressure the blood flow had been reduced below the control value: in a few cases it appeared also without a preceding flow reduction. In almost all cases there was a marked tendency to normalization of the blood flow after the initial period of hyperemia. No chemical factors in the artificial cerebrospinal fluid could be made responsible for the phenomenon described, which is attributed to a disturbance of cerebrovascular function, impairing the ordinary flow autoregulation.

Prolonged cerebral hyperemia after periods of increased cerebrospinal fluid pressure in dogs.

The effects of repeated subarachnoid hemorrhages have been investigated experimentally in dogs. The main objectives were to determine the tolerance to repeated hemorrhage and to study the changes occurring during the repeated bleeds, in intracranial pressure, EEG, ECG, systemic arterial pressure and respiration. The natural course of an intracranial hemorrhage was simulated by shunting blood from a femoral artery through a drop recorder into five different sites in the craniospinal system: the chiasmatic cistern, a lateral ventricle, the cisterna magna, the lumbar subarachnoid space and into the cerebral tissue of the left frontal lobe. The hemorrhage was allowed to continue until it stopped spontaneously. Each bleed resulted in a transient rise in intracranial pressure to the level of the arterial pressure, followed by a return to a steady state value. The time taken for the attainment of the steady state was increasingly prolonged. The final steady state pressure increased with each bleed. Ultimately, a stage was reached where the hemorrhage resulted in a sustained high pressure at the level of the arterial blood pressure, producing failure of vital functions and an irreversibly isoelectric electroencephalogram. The average number of bleeds necessary to produce this state in the case of hemorrhage into brain parenchyma was 3 (range 2-4), into the lateral ventricle, 4 range 3-5), and into the cisterna chiasmatica, 5 (range 2-7). After 5 hemorrhages into the cisterna magna and the spinal subarachnoid space, a local resistance at the bleeding site was built up which prevented further bleeding.

Jan Löfgren

Papers

The pressure-volume curve of the cerebrospinal fluid space in dogs

Cranial and spinal components of the cerebrospinal fluid pressure‐volume curve

Effects of varied cerebrospinal fluid pressure on cerebral blood flow in dogs.

Prolonged cerebral hyperemia after periods of increased cerebrospinal fluid pressure in dogs.

Characteristics and limits of tolerance in repeated subarachnoid hemorrhage in dogs.