Indomethacin and cerebral autoregulation in severe head injured patients: a transcranial Doppler study

Summary Objective. To assess the effect of indomethacin on cerebral autoregulation, systemic and cerebral haemodynamics, in severe head trauma patients. Design. Prospective, controlled clinical trial, with repeated measurements. Settings. A 12-bed adult general intensive care unit in a third level referral university hospital. Patients. 16 severely head injured patients, 14 males, age range 17–60. Interventions. Indomethacin was administrated as a load plus continuous infusion. Indomethacin reactivity was assessed as the estimated cerebral blood flow change elicited by the load. Dynamic and static cerebral autoregulation tests were performed before indomethacin administration, and during its infusion. Measurements and main results. Systemic and cerebral haemodynamic changes were assessed through continuous monitoring of mean arterial pressure, transcranial Doppler cerebral blood flow velocity, intracranial pressure, cerebral perfusion pressure, and jugular venous oxygen saturation. Indomethacin loading dose was immediately followed by a cerebral blood flow median decrease of 36 or 29% (p = ns) evaluated by two different methods, by an ICP decrease and by an AVDO₂ increase from 3.52 to 6.15 mL/dL (p = 0.002). Dynamic autoregulation increased from a median of 28 to 57% (p<0.05) during indomethacin infusion; static autoregulation also increased, from a median of 72 to 89% (p = ns). Conclusions. Indomethacin decreased intracranial pressure and cerebral blood flow, and increased cerebral perfusion pressure, while maintaining tissue properties of further extracting O₂. The increase in both autoregulatory values reveals an enhancement of cerebral microvasculature reactivity under indomethacin, during hypertensive and – especially – during hypotensive situations.     

Brain swelling and brain oedema in acute head injury

Summary Chronological changes in diffuse brain swelling and brain oedema were studied in repeated CT studies following a closed head injury. These findings were compared with changes in intracranial pressure (ICP). The grades of diffuse brain swelling were classified into mild, moderate and marked according to the CT findings. Planimetry of low density areas of brain oedema was carried out on repeated CT images. Diffuse brain swelling was recognized in 71 of patients shortly after the head injury and subsided within days 3–5. Brain oedema first appeared 24 hours post injury and did not reach its maximum size and distribution before days 5–8. Thus, these two events can be clearly separated. The intracranial pressure reflected the course of the brain swelling and was not very high during the presence of maximum oedema.     

Middle cerebral artery transcranial doppler velocity monitoring during orthotopic liver transplantation: Changes at reperfusion—A report of six cases

Study Objective: To determine the effect of reperfusion of the grafted liver on transcranial Doppler blood flow velocity in the middle cerebral artery in humans during orthotopic liver transplantation.

Design: Clinical study.

Setting: University hospital.

Patients: 6 patients scheduled for orthotopic liver transplantation.

Interventions: Middle cerebral artery blood flow velocity (MCAVm) was monitored continuously using a transcranial Doppler (TCD) probe. The TCD measurements were noninvasive.

Measurements and Main Results: The EME TC2000S TCD probe (Nicolet, Inc., Memphis, TN) was secured to the head using a strap providing continuous measurement of MCAVm. All other data were recorded by a patient monitoring system and a respiratory gas analyzer. Averaged MCAVm increased significantly in 5 of 6 patients (p < 0.001) when pre-reperfusion and post-reperfusion values were compared. Maximum post-reperfusion values for MCAVm, pulsatility index (PI), and systolic Doppler velocity (Vs) were greater than the corresponding immediate pre-reperfusion values (p < 0.05, p < 0.05, and p < 0.001, respectively). The increases in MCAVm cannot be explained on the basis of hypercarbia alone and were observed in the presence of systemic arterial hypotension and abrupt increases in central venous pressure, particularly at the time of graft reperfusion.

Conclusions: MCAVm increased with reperfusion of the grafted liver. These data suggest that multiple factors—including hypercarbia, lactic acidosis, or multiple vasoactive substances released by the grafted liver—may contribute to the observed increases in MCAVm, Vs, and PI.     

Haemodynamic patterns in children with posttraumatic diffuse brain swelling. A preliminary study in 6 cases with neuroradiological features consistent with diffuse axonal injury

Summary Background. In the present report we describe the cerebral haemodynamics and the neuroradiological findings observed in six consecutive children, three males and three females aged 4–15.6 yrs (mean age 8.95) displaying a neuroradiological pattern consistent with diffuse axonal injury (DAI) along with slit ventricles. Methods. All the patients were admitted to the Paediatric Intensive Care Unit with GCS scores less than 8 after a severe brain injury. Serial head computed to mography (CT) and magnetic resonance (MR) scans demonstrated a radiological pattern of DAI. Transcranial Doppler Sonography (TCD) of the middle cerebral arteries was performed through the temporal bone window in all the patients. All patients but one underwent a continuous monitoring of intracranial pressure (ICP) and cerebral extraction of O₂ (CEO₂). Treatment with barbiturates and hyperventilation was necessary in all the cases. In one patient, a bilateral decompressive cran iectomy was performed in order to decrease severe in tracranial hypertension. Results. Hyperflow along with intracranial hyper tension, variably responsive to barbiturate medication, was observed in all the patients by means of TCD and CEO₂. Conclusions. Intracranial hypertension can be elevated in pediatric posttraumatic hyperflow syndromes associated with DAI. The observation of the time course of the parameters studied allowed us to modify the pharmacological treatment and/or perform surgical decompression (external cerebrospinal fluid (CSF) drainage in five cases; decompressive craniectomy in one case). Compartmental hyperflow TCD pattern was evident in only one patient. Although the limited number of pa tients in our series does not allow definite conclusions, we strongly believe that TCD, with ICP and CEO₂ monitoring, are useful tools in planning surgical strategy in children with neuroradiological signs of DAI.     

双侧开颅在重型颅脑损伤术中急性脑膨出的应用

目的 探讨重度颅脑损伤急性脑膨出的原因及最佳治疗方案.方法 回顾性分析26例采用双侧开颅治疗重度颅脑损伤术中急性脑膨出患者的临床资料.结果 恢复良好4例,中残5例,重残2例,植物生存3例,死亡12例.结论 迟发性颅内血肿和急性弥漫性脑肿胀是颅脑损伤开颅术中急性脑膨出的主要原因,而采用双侧开颅可明显提高抢救成功率和患者的生存质量.     

Indication for invasive diagnostic studies and surgical therapy in cerebral ischemia,based on results of non-invasive transcranial Doppler sonography

In order to better define patients who might benefit from cerebral revascularization surgery, transcranial Doppler sonography was used in more than 480 patients. Thus invasive diagnostic studies could be limited to probable surgical candidates. Transcranial Doppler sonography has proven to be reliable for the study of the degree of efficacy of intracranial collateral pathways in hemodynamic borderline situations. Over the last 4 years, the application of the algorythm presented in this paper resulted in a reduction of the number of candidates for surgical revascularization to 19.     

Analysis of abnormal jugular bulb oxygen saturation data in patients with severe head injury

Summary Jugular bulb oximetry provides the first bedside, continuously available information on cerebral perfusion adequacy. An extensive analysis was made of all jugular bulb oxygen saturation (SjO₂) data obtained in 50 patients suffering from severe head injury. A total of 176 periods (more than 30 minutes) with reliable, abnormal SjO₂-values was observed, with 62 desaturation periods (SjO₂ < 55%) and 114 high SjO₂-periods (SjO₂ > 80%). Jugular desaturation periods were predominantly observed in the first 2 days of monitoring and seemed the most closely correlated to lowered cerebral perfusion pressure and lowered arterial carbon dioxide tension. The high SjO₂-values were more equally distributed over the first 5 days of monitoring and seemed mostly correlated to increased arterial carbon dioxide tension. Highlights of the general management of severely head injured patients is discussed, focussing attention on the importance of cerebral perfusion pressure and normoventilation.     

重型颅脑损伤患者心肌损害的早期诊断

目的 探讨重型颅脑损伤患者心肌损害的早期诊断及心脏型脂肪酸结合蛋白(h-FABP)对患者预后的影响.方法 血清h-FABP采用双抗体夹心酶联免疫一步法定量检测,cTnI采用固相酶联免疫吸附试验(ELISA),CK-MB采用免疫抑制法.结果 重型颅脑损伤患者组血清h-FABP、cTnI及CK-MB水平分别显著高于健康对照组(P<0.01),重型颅脑损伤患者血清h-FABP阳性率显著高于血清cTnI、CK-MB或心电图的阳性率(P<0.01),47例重型颅脑损伤患者治疗后死亡8例,病死率为17.02%(8/47),血清h-FABP、cTnI及CK-MB异常组的病死率显著高于正常组(P<0.01);重型颅脑损伤患者血清h-FABP预测发生死亡具有高的敏感性和阴性预测值,但特异性和准确度较低.结论 血清h-FABP定量测定作为一种对微小心肌损伤高敏感的指标,可作为判断重型颅脑损伤急性期病情轻重、评价发生意外的一项客观指标.     

The relationship between cerebral metabolic rate of oxygen and cerebral blood flow in the acute phase of head injury

In 20 comatose patients (Glasgow coma scale less than or equal to 6 at admission) with severe head injury, the cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of the hemispheric cerebral blood flow (CBF) and the arterio-venous oxygen content difference (AVDO2). The hemispheric CBF was calculated by the intracarotid 133xenon washout method by stochastic analysis as the average of 16 regions, and the measurements were performed within 3 weeks after the acute trauma. Generally no significant correlation (P less than 0.05) between CMRO2 and CBF was found, either in the total number of paired observations, in studies of hyperaemia defined as CBF greater than or equal to 30 ml 100 g-1 min-1; or in studies with reduced flow (CBF less than 30 ml 100 g-1 min-1). However, in about 50% of patients subjected to repeated studies within days, CBF was positively correlated to CMRO2, and this correlation was observed independently of the CBF value. Hyperaemia was associated with a significant decrease in AVDO2, a significant increase in both absolute and relative CO2 reactivity, and a significant increase in ventricular fluid pH; but not to an increase in intraventricular pressure, mean arterial blood pressure or significant changes in ventricular fluid lactate or lactate/pyruvate ratio.     

The use of indomethacin to treat acute rises of intracranial pressure and improve global cerebral perfusion in a child with head trauma

Background: The use of vasoconstrictors (e.g. dihydroergotamine, indomethacin) for the treatment of increased intracranial pressure (ICP) secondary to brain trauma is controversial. In particular, it has been suggested that vasoconstrictors be employed only for intracranial hypertension secondary to hyperemia, when venous jugular bulb saturation (SjO₂) is >75%. Method We administered indomethacin as a bolus i.v. (5–10 mg) on 18 occasions to a multiple-injured 3-year-old child with acute rises of ICP secondary to severe brain trauma (GCS score 7) determining a large hypodensity area in and swelling of the right hemisphere. Results: Before indomethacin administration the average of mean ICP was 68.1 ± 10.8 (SD) mm Hg (range 47–84) and the cerebral perfusion pressure (CCP) was 38.4±10.4 mm Hg (range 30–65). In response to indomethacin, ICP dropped in a few seconds to 22.7±5.6 and CCP increased to 82.4±6.1 mm Hg (P <0.001), while the mean arterial pressure remained unchanged. On 6 occasions SjO₂ was also evaluated immediately before and 5 and 10 min after indomethacin administration. Before indomethacin administration, SjO₂ values were within the normal range on 2 occasions and abnormally low on four. SjO₂ increased from the mean value of 45.6215.7 to 59.828.9 (after 5 min) and 60.6212.4% (after 10 min) (P< 0.01 versus pre-indomethacin). At the same time the cerebral venous pH increased from 7.4320.01 to 7.4550.01 (P=0.01). These findinge suggest that the global cerebral perfusion was improved. Eighteen days after injury the child was awake and was discharged from the ICU. Conclusion: To our knowledge, increase of SjO, in response to indomethacin has not been previously reported. Although great caution is necessary in the use of indomethacin for the treatment of ICE these findings suggest that indomethacin can be useful for the treatment of acute rises of ICP compromising severely the CCP, even if SjO, is normal or abnormally low. Under these circumstances, indomethacin can improve the global cerebral perfusion.     

Traumatic aneurysms of cerebral arteries a study of five cases

Summary Five cases of traumatic aneurysms of cerebral arteries are presented, two located at the internal carotid artery, and three at peripheral arterial branches.The manifestation of the aneurysm was a delayed neurological deterioration due to bleeding from the aneurysm, 4–35 days (mean 21 days) after the head trauma; four patients had an intracerebral haematoma and one patient had a subarachnoid haemorrhage. One patient died from extensive cerebral injuries with the aneurysm untreated. In four cases the aneurysm was treated surgically. Three patients returned to their former occupation and one patient died from late septic complications.It is concluded that signs of delayed intracranial bleeding after a head trauma should raise the suspicion of an underlying traumatic aneurysm, and in addition to a CT-scan an angiography should be performed.     

The future role of neurosurgery in the care of head injuries

Summary Head injuries are major cause of death and disability under the age of 45 years even in developing countries. Mortality and morbidity are frequently due to avoidable secondary brain damage in patients whose initial injury was not very severe. Optimal care depends on neurosurgeons defining clear management policies for injuries of all severities so that other surgeons know which patients need neurosurgical care and know how to deal with the others. More patients need to go to neurosurgeons; only specialized centers dealing with many cases can develop advanced clinical skills and have the capability to carry out major clinical research. In the competitive world of high technology medicine neurosurgery needs to deliver good care for head injuries in the community as a whole if it is to attract substantial support.     

The effects of indomethacin on intracranial pressure,cerebral blood flow and cerebral metabolism in patients with severe head injury and intracranial hypertension

Summary In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control intracranial pressure (ICP) (ICP>20 mmHg) by artificial hyperventilation (PaCO₂ level 3.5–4.0 kPa) and barbiturate sedation, indomethacin was used as a vasoconstrictor drug. In all patients, indomethacin (a bolus injection of 30 mg, followed by 30 mg/h for seven hours) reduced ICP below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in CBF at 2h. After 7h, ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In the other patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. These results suggest that indomethacin due to its cerebral vasoconstrictor and antipyretic effect should be considered as an alternative for treatment of ICP-hypertension in head-injured patients.Presented at the Fifth Nordic CBF Symposium, Lund, Sweden, 21–22 May 1990.     

Phase shift and correlation coefficient measurement of cerebral autoregulation during deep breathing in traumatic brain injury (TBI)

Summary Background. Impairment of cerebral autoregulation is known to adversely affect outcome following traumatic brain injury (TBI). The phase shift (PS) method of cerebral autoregulation (CA) assessment describes the time lag between fluctuations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) in the middle cerebral artery. An alternative method (Mx-ABP) is based on the statistical correlation between ABP and CBFV waveforms over time. We compared these two indices in a cohort of severely head injured patients undergoing controlled, 6-breaths-per-minute ventilation. Methods. PS and Mx-ABP were calculated from 33 recordings of CBFV and MAP in 22 patients with TBI. Spearman’s correlation coefficient was used to assess the agreement between PS and Mx-ABP. The relationship between ICP slow wave amplitude, MAP slow wave amplitude and mean ICP was also examined. Findings. Mean values for Mx-ABP and PS were 0.44 ± 0.27, and 49 ± 26 (degrees), respectively. PS correlated significantly with Mx-ABP (r = −0.648, p < 0.001). A Bland-Altman plot of normalised Mx-ABP and Phase Shift values showed no significant bias or relationship (mean difference = 0.0004, r = −0.037, p = 0.852). During the test procedure, ICP fluctuated in an approximately sinusoidal fashion, with a mean amplitude of 4.96 ± 2.72 mmHg (peak to peak). The magnitude of ICP fluctuation during deep breathing correlated weakly but significantly with mean ICP (r = 0.391, p < 0.05) and with the amplitude of ABP fluctuations (r = 0.625, p < 0.0005). Conclusions. Phase shift and Mx-ABP in TBI are well correlated. Deep breathing presents as an effective tool with which to assess autoregulation using the phase shift method. Correspondence: Philip M. Lewis, BappSc, Scientific Officer, Department of Neurosurgery, Alfred Hospital, P.O. Box 315, Prahran, VIC 3181, Australia.     

Brain tissue pO2 in relation to cerebral perfusion pressure,TCD findings and TCD-CO2-reactivity after severe head injury

Summary As a reliable continuous monitoring of cerebral blood flow and/or cerebral oxygen metabolism is necessary to prevent secondary ischaemic events after severe head injury (SHI) the authors introduced brain tissue pO₂ (ptiO₂) monitoring and compared this new parameter with TCD-findings, cerebral perfusion pressure (CPP) and CO₂-reactivity over time on 17 patients with a SHI. PtiO₂ reflects the balance between the oxygen offered by the cerebral blood flow and the oxygen consumption by the brain tissue. According to TCD-CO₂reactivity PtiO₂-CO₂-reactivity was introduced.After initally (day 0) low mean values (ptiO₂ 7.7 +/–2.6 mmHg, TCD 60.5 +/–32.0 cm/sec and CPP 64.5 +/–16.0 mmHg/, ptiO₂ increased together with an increase in blood flow velocity of the middle cerebral artery and CPP. The relative hyperaemic phase on days 3 and 4 was followed by a decrease of all three parameters. Although TCD-CO₂-reactivity was except for day 0 (1.4+/–1.5%), sufficient. ptiO₂-CO₂-reactivity sometimes showed so-called paradox reactions from day 0 till day 3, meaning an increase of ptiO₂ on hyperventilation. Thereafter ptiO₂-CO₂-reactivity increased, increasing the risk of inducing ischaemia by hyperventilation.The authors concluded that ptiO₂-monitoring might become an important tool in our treatment regime for patients requiring haemodynamic monitoring.     

Hyperemia prior to acute brain swelling during rewarming of patients who have been treated with moderate hypothermia for severe head injuries

OBJECT: The goal of this study was to elucidate the optimal time for rewarming of patients who have been treated with hypothermia for severe head injury. METHODS: Eleven patients with severe head injuries who had been treated by hypothermia underwent transcranial Doppler (TCD) ultrasonography examinations. The patients were divided into two groups: Group A consisted of three patients in whom acute brain swelling occurred during the rewarming period and Group B was composed of eight patients who displayed no significant intracranial hypertension during or after hypothermia therapy. In all patients, the mean flow velocity of the middle cerebral artery (FV(MCA)) recorded transcranially and the mean flow velocity of the internal carotid artery (FV(ICA)), recorded high in the neck, were monitored at 24-hour intervals after the patient was admitted to the hospital. In Group A, the FV(MCA) was normal at 48 hours (maintenance state of hypothermia) in each patient, and abnormal increases and peak values (> 100 cm/second) occurred from 96 to 144 hours postinjury (rewarming period). The FV(ICA), which was monitored concurrently also varied as the FV(MCA) increased. The pulsatility indices in the arteries decreased at the time of the peak FV(MCZ). The enhanced FV(MCA) was consistent with hyperemia because of the low FV(MCA)/FV(ICA) ratios (< 3). Two patients in whom jugular venous oxygen saturation was monitored were found to have high values (> 80%), representing hyperemia. All intracranial pressures (ICPs) that lay within the normal range at 48 hours postinjury elevated acutely after the peak FV(MCA). In Group B, both FV(MCA) and FV(ICA) values were normal at 48 hours postinjury and remained stable throughout the rewarming period. Values of ICP were also maintained within the normal range until the patients were weaned from hypothermia therapy. CONCLUSIONS: Hyperemia, detectable by TCD ultrasonography, may serve as an index in the prediction of acute brain swelling, and rewarming should be terminated when such a hemodynamic phenomenon is observed.     

Effects of magnesium sulphate on cerebral haemodynamics in healthy volunteers: a transcranial Doppler study

Background. Magnesium is increasingly being considered as aneuroprotective agent. We aimed to study its effects on middlecerebral artery blood flow velocity (V_mca), cerebral autoregulationand cerebral vascular reactivity to carbon dioxide (CRCO₂) inhealthy volunteers. Methods. Fifteen healthy volunteers were recruited. Using transcranialDoppler ultrasonography, V_mca was recorded continuously. Thestrength of autoregulation was assessed by the transient hyperaemicresponse test, and the CRCO₂ was measured by assessing changesin V_mca to the induced changes in end-tidal carbon dioxide.I.V. infusion of magnesium sulphate was then started (loadingdose of 16 mmol followed by an infusion at the rate of 2.7 mmolh^–1) for 45 min. The cerebral haemodynamic variables weremeasured again near the end of the infusion of magnesium sulphate. Results. Total serum magnesium levels were doubled by the infusionregimen. However, there were no significant changes in V_mca,strength of autoregulation, or CRCO₂. Five of the volunteersreported marked nausea and two developed significant hypotensionduring the loading dose. Conclusions. Infusion of magnesium sulphate, in a dose thatdoubles its concentration in plasma, does not affect V_mca, strengthof autoregulation or CRCO₂ in healthy volunteers. However, itcan be associated with nausea and hypotension. Br J Anaesth 2003; 91: 273–5     

重型颅脑损伤术中急性脑膨出原因及防治

目的探讨重型颅脑损伤术中急性脑膨出的形成原因及有效的防治措施。方法回顾性分析76例重型颅脑损伤患者术中出现急性脑膨出的原因及防治措施的疗效。结果迟发性颅内血肿、弥漫性脑肿胀、侧裂区脑挫裂伤、脑疝后脑梗塞、呼吸道梗阻等是颅脑损伤术中急性脑膨出的主要原因。结论术中出现急性脑膨出的原因有多种,应及时复查头部CT,明确病因,准确处理,提高疗效。     

Does acute hyperventilation provoke cerebral oligaemia in comatose patients after acute head injury?

Summary In 27 comatose patients with acute head injury, 45 paired studies of regional cerebral blood flow (rCBF) were performed before and after hyperventilation. In total 676 regions were studied, and rCBF was calculated as initial slope index using the intracarotid washout technique of 133 Xe. The tests were applied from one day to three weeks after the acute trauma.In total hyperventilation from PaCO₂ averaging 4.8 to 3.5 kPa increased the frequency of regions with oligaemia defined CBF<20ml/100g/min from 5 to 16%. Before hyperventilation oligaemia was observed in 11 of 45 studies (9 of 27 patients); after hyperventilation the frequency increased to 21 studies (15 patients). The frequency of severe oligaemia (CBF<15 ml) increased from 0.1 to 3% of all regions, or from 2 to 8 of all studies (from 2 to 9 patients). The increased frequency of oligaemia after hyperventilation was correlated to a poor outcome (dementia, vegetative survival or death), where it was observed in 21% of all regions, in 16 of 26 studies and 11 of 15 patients, whereas the frequency in patients with a good recovery was found to be 7% of all regions and observed in 5 of 19 studies (4 of 12 patients). The high frequency of oligaemia after hyperventilation was associated to a low hemispheric CBF before hyperventilation, but not to the level of PaCO₂, the level of intracranial pressure, cerebral perfusion pressure or CSF-pH or lactate.These findings strongly suggest that acute hyperventilation might be controversial as it provokes a decrease in rCBF close to ischaemic threshold, especially in patients with reduced rCBF prior to acute hyperventilation. Furthermore, it suggest that rCBF<20 ml indicate a poor outcome.