Jam Ghajar

Survey of critical care management of comatose, head-injured patients in the United States

OBJECTIVE This survey was designed to study current practices in the monitoring and treatment of patients with severe head injury in the United States. DATA SOURCES The collected data represent answers to telephone interviews of nurse managers, clinical specialists, and staff nurses specializing in neurotrauma care at 277 randomly selected hospitals from a total pool of 624 trauma centers. Overall, 261 (94%) centers participated in the survey. Of the participating centers, 219 (84%) were providers of care for severely head-injured patients. In order to assess reliability and account for differences among respondents, personnel from 40 (15%) centers were resurveyed 6 months later and a different nursing professional was interviewed, although the questions remained the same. DATA EXTRACTION The largest group of respondents came from level I centers (49%), followed by level II (32%) and level III (2%). Thirty-four percent of the surveyed hospitals had a designated neurologic/neurosurgical intensive care unit, and 24% of all units surveyed were under the direction of either a neurosurgeon or a neurologist. Twenty-eight percent of the centers routinely performed intracranial pressure monitoring, while 7% of the centers reported never using this technique. The use of ventriculostomy catheters for intracranial pressure monitoring was employed in 72% of the centers, but cerebrospinal fluid drainage was utilized by only 44% of the hospitals. The percentage of patients who had their intracranial pressure monitored was significantly higher in level I trauma centers and at hospitals that treated larger numbers of severely head-injured patients (15 to 30 patients per month, which represented 15% of the hospitals surveyed). Hyperventilation and osmotic diuretics were used in 83% of centers to reduce intracranial hypertension. The administration of barbiturates was reported in 33% of the units as a treatment for intracranial hypertension. Corticosteroids were used more than half of the time in 64% of trauma centers. Twenty-nine percent of the centers reported aiming for PaCO2 values of < 25 torr (< 3.3 kPa). CONCLUSIONS The survey data indicate that there is a considerable variation in the management of patients with severe head injury in the United States. The establishment of guidelines for the management of head injury based on available scientific data and moderated by practical and financial considerations may lead to improvement in the standard of care.

Hypertonk/Hyperoncotic Saline Reliably Reduces ICP in Severely Head-Injured Patients with Intracranial Hypertension

Hypertonic saline (HS) has been shown to decrease intracranial pressure (ICP) and cerebral water content in experimental models of traumatic brain injury (TBI). The purpose of the present study was to test the efficacy of administration of HS (7.5%) combined with 6% hydroxyethyl starch (molecular weight 200.000/0.60-0.66; HHES) for the treatment of therapy-resistant intracranial hypertension in patients with severe TBI. Six patients with severe TBI (GCS < 8) who met the inclusion criteria (therapy resistant ICP > 25 mmHg, cerebral perfusion pressure (CPP) < 60 mmHg, plasma-Na+ < 150 mOsm and > 4 hours since the last HS/HHES treatment) were prospectively enrolled in the study and received between one and ten bolus infusions of maximal 250 ml HS/HHES at a rate of 20 ml/min. A total of 32 infusions were given. Administration of HS/HHES significantly lowered ICP by 44% and improved CPP by 38% to well above 70 mmHg at 30 min without affecting arterial blood pressure or blood gases. Plasma sodium normalized within 30 min. Experimental studies from our laboratory indicate that the ICP lowering effect is primarily due to dehydration of brain tissue and that cerebral blood volume remains largely unaffected by HS. In summary, HS/HHES reduces otherwise therapy-resistant intracranial hypertension and improves cerebral perfusion even after repeated administration without negatively affecting blood pressure or causing a rebound ICP increase.

Traumatic injury induces interleukin-6 production by human astrocytes

The brain is being evaluated as a de novo source of cytokines. Because recent evidence indicates that interleukin-6 (IL-6) may influence blood-brain barrier function and vascular permeability, we have sought to determine whether mechanical injury can directly induce in situ cerebral IL-6 production. Adult human astrocyte cultures were subjected to mechanical injury by the in vitro method of fluid percussion barotrauma, developed in our laboratory. Serial supernatant samples were collected for 8 h and evaluated for IL-6 activity using a proliferation assay employing the dependent B cell hybridoma cell line, B9. At optimum injury, the IL-6 level became significantly (P < 0.0001, analysis of variance) elevated from baseline 2 h after trauma and continued to increase over the observation period. Our study shows that following mechanical injury human astrocytes produce IL-6, which may contribute to post-traumatic cerebrovascular dysfunction. Elucidating the precise role of intracerebral cytokines is essential to our understanding of the mechanism responsible for post-traumatic cerebrovascular dysfunction.

Early White Blood Cell Dynamics After Traumatic Brain Injury: Effects on the Cerebral Microcirculation

Increasing clinical and experimental evidence suggests that traumatic brain injury (TBI) elicits an acute inflammatory response. In the present study we investigated whether white blood cells (WBC) are activated in the cerebral microcirculation early after TBI and whether WBC accumulation affects the posttraumatic cerebrovascular response. Twenty-four anesthetized rabbits had chronic cranial windows implanted 3 weeks before experimentation. Animals were divided into four experimental groups and were studied for 7 hours (groups I, IIa, and III) or 2 hours (group IIb). Intravital fluorescence videomicroscopy was used to visualize WBC (rhodamine 6G, intravenously), pial vessel diameters, and blood–brain barrier (BBB) integrity (Na+-fluorescein) at 6 hours (groups I, IIa, and III) or 1 hour (group IIb) after TBI. Group I (n = 5) consisted of sham-operated animals. Groups IIa (n = 7) and IIb (n = 5) received fluid-percussion injury at 1 hour. Group III (n = 7) received fluid-percussion injury and 1 mg/kg anti–adhesion monoclonal antibody (MoAb) “IB4” 5 minutes before injury. Venular WBC sticking, intracranial pressure (ICP), and arterial vessel diameters increased significantly for 6 hours after trauma. IB4 reduced WBC margination and prevented vasodilation. Intracranial pressure was not reduced by treatment with IB4. Blood–brain barrier damage occurred at 1 hour but not at 6 hours after TBI and was independent of WBC activation. This first report using intravital videomicroscopy to study the inflammatory response after TBI reveals upregulated interaction between WBC and cerebral endothelium that can be manipulated pharmacologically. White blood cell activation is associated with pial arteriolar vasodilation. White blood cells do not induce BBB breakdown less than 6 hours after TBI and do not contribute to posttraumatic ICP elevation. The role of WBC more than 6 hours after TBI should be investigated further.

Blood-Brain Barrier Breakdown Occurs Early After Traumatic Brain Injury and is not Related to White Blood Cell Adherence

The time course of blood-brain barrier (BBB) breakdown after traumatic brain injury (TBI) has important implications for therapy. This study was conducted in order to test post-traumatic BBB dysfunction in a model of fluid-percussion induced TBI in rabbits at 1 and 6 hours after TBI and relate it to white blood cell (WBC) activation. Ten anesthetized rabbits had chronic cranial windows implanted three weeks prior to experimentation. Fluid-percussion injury (3.5 atm.) was induced and animals were followed for 1 or 6 h. Intravital fluorescence videomicroscopy was used to assess BBB permeability and WBC adhesion to pial venules. Na(+)-fluorescein was infused continuously over 30 min at either 30 min (Group I, n = 5) or 5.5 h (Group II, n = 5) after TBI. Microvascular permeability in individual postcapillary venules was assessed qualitatively at 1 and 30 min after start of infusion. TBI led to a transient mean arterial blood pressure (MAP) surge after trauma and a progressive increase in the number of sticking WBCs per mm2 vessel wall. Na(+)-fluorescein extravasation was observed in 4 out of 5 Group I animals and in none of Group II. BBB breakdown was not associated with WBC sticking. We conclude that after fluid-percussion injury the BBB is damaged at 1 h post-trauma and that its function is restored 6 h later. Increased WBC sticking at 6 h is not associated with BBB breakdown. Whether WBCs may cause vascular permeability changes at a later point needs further investigation.

A Square Signal Wave Method for Measurement of Brain Extra- and Intracellular Water Content

Brain tissue electrical impedance is a commonly used method to evaluate the dynamics of brain edema. We have found the square wave impedance method simpler and more cost-effective than the currently used sine wave impedance method. This square wave method avoids the necessity for expensive frequency control and amplitude-phase measuring devices as well as simplifying on-line data processing. In our experiments the electrical impulse was generated by a pulse generator of Macintosh data acquisition system. The signal (I = 11 muA, t = 2-20 ms) was delivered every 2-3 s external electrodes of a tetrapolar system through a specially designed isolation-calibration device. This electrode system was inserted into the cerebral cortex of experimental animals (rat). The cerebral cortex was found to have linear electrical properties in the 5-30 muA range. Our impedance measurement system was tested in calibration trials, and showed system reliability and accuracy. The system was also tested in pilot experiments, in vivo, in a rat brain osmotic edema model.

The Role of LTC4 in the Development of Post-Traumatic Intracranial Hypertension

A complex series of pathophysiologic events follow the initial transfer of mechanical energy in traumatic brain injury, and constitute the secondary phenomena which are responsible for the development of intracranial hypertension. Elevation of intracranial pressure is the hallmark of post-traumatic cerebrovascular dysfunction, and reflects some combination of vasomotor dysfunction and vascular permeability abnormalities which result in a net increase in the total intracranial volume. Considerable evidence exists in the literature which demonstrates that following mechanical brain injury, local and regional abnormalities in perfusion occur, characterized by either hyperemia or ischemia [1,7]. It remains unclear, however, which of these dysfunctional vascular states is responsible for the irreparable tissue damage which occurs in the first 96 hours following injury. Obviously, the goal of therapeutics aimed at preserving potentially viable brain tissue following injury is centered around optimizing oxygen and substrate delivery to the salvagable tissue and interrupting the propagation of pathophysiologic events which subject the brain to secondary ischemic injury.