Efficacy of the All-in-One Therapeutic Strategy for Severe Traumatic Brain Injury: Preliminary Outcome and Limitation / 대한신경손상학회지

OBJECTIVE: Despite recent advances in medicine, no significant improvement has been achieved in therapeutic outcomes for severe traumatic brain injury (TBI). In the treatment of severe multiple traumas, accurate judgment and prompt action corresponding to rapid pathophysiological changes are required. Therefore, we developed the “All-in-One” therapeutic strategy for severe TBI. In this report, we present the therapeutic concept and discuss its efficacy and limitations. METHODS: From April 2007 to December 2015, 439 patients diagnosed as having traumatic intracranial injuries were treated at our institution. Among them, 158 patients were treated surgically. The “All-in-One” therapeutic strategy was adopted to enforce all selectable treatments for these patients at the initial stages. The outline of this strategy is as follows: first, prompt trepanation surgery in the emergency room (ER); second, extensive decompression craniotomy (DC) in the operating room (OR); and finally, combined mild hypothermia and moderate barbiturate (H-B) therapy for 3 to 5 days. We performed these approaches on a regular basis rather than stepwise rule. If necessary, internal ecompression surgery and external ventricular drainage were performed in cases in which intracranial pressure could not be controlled. RESULTS: Trepanation surgery in the ER was performed in 97 cases; among these cases, 46 had hematoma removal surgery and also underwent DC in the OR. Craniotomy was not enforced unless the consciousness level and pupil findings did not improve after previous treatments. H-B therapy was administered in 56 cases. Internal decompression surgery, including evacuation of traumatic intracerebral hematoma, was additionally performed in 12 cases. Three months after injury, the Glasgow Outcome Scale (GOS) score yielded the following results: good recovery in 25 cases (16%), mild disability in 28 (18%), severe disability in 33 (21%), persistent vegetative state in 9 (6%), and death in 63 (40%). Furthermore, 27 (36%) of the 76 most severe patients who had an abnormal response of bilateral eye pupils were life-saving. Because many cases of a GOS score of ≤5 are included in this study, this result must be satisfactory. CONCLUSION: This therapeutic strategy without any lose in the appropriate treatment timing can improve the outcomes of the most severe TBI cases. We think that the breakthrough in the treatment of severe TBI will depend on the shift in the treatment policy.

Life-Threatening Dyskalaemia after Barbiturate Coma Therapy: The Strategy of Management

Barbiturate coma therapy (BCT) is a treatment option that is used for refractory intracranial hypertension after all other options have been exhausted. Although BCT is a brain protection treatment, it also has several side effects such as hypotension, hepatic dysfunction, renal dysfunction, respiratory complications and electrolyte imbalances. One less concerning but potentially life-threatening complication of BCT is dyskalaemia. This complication could present as severe refractory hypokalaemia during the therapy with subsequent rebound hyperkalaemia after cessation of the therapy. Judicious potassium replacement during severe refractory hypokalaemia and gradual cessation of the therapy to prevent rebound hyperkalaemia are recommended strategies to deal with this complication, based on previous case series and reports. In this case report, we show that these strategies were applicable in improving severe hypokalaemia and preventing sudden, life-threatening rebound hyperkalaemia. However, even with use of these strategies, BCT patients could still present with mild, asymptomatic hyperkalaemia.

A Fatal Adverse Effect of Barbiturate Coma Therapy: Dyskalemia / 대한신경손상학회지

The management guideline for traumatic brain injury (TBI) recommends high-dose barbiturate therapy to control increased intracranial pressure refractory to other therapeutic options. High-dose barbiturate therapy, however, may cause many severe side effects; the commonly recognized ones include hypotension, immunosuppression, hepatic dysfunction, renal dysfunction, and prolonged decrease of cortical activity. Meanwhile, dyskalemia remains relatively uncommon. In this study, we report the case of a hypokalemic patient with severe rebound hyperkalemia, which occurred as a result of barbiturate coma therapy administered for TBI treatment.

Status Epilepticus Caused by Nefopam

Nefopam, a centrally acting analgesic, has been used to control postoperative pain. Reported adverse effects are anticholinergic, cardiovascular or neuropsychiatric. Neurologic adverse reactions to nefopam are confusion, hallucinations, delirium and convulsions. There are several reports about fatal convulsive seizures, presumably related to nefopam. A 71-year-old man was admitted for surgery for a lumbar spinal stenosis. He was administered intravenous analgesics : ketorolac, tramadol, orphenadrine citrate and nefopam HCl. His back pain was so severe that he hardly slept for several days; he even needed morphine and pethidine. At 4 days of administration of intravenous analgesics, the patient suddenly started generalized tonic-clonic seizures for 15 seconds, and subsequently, status epilepticus; these were not responsive to phenytoin and midazolam. After 3 days of barbiturate coma therapy the seizures were controlled. Convulsive seizures related to nefopam appear as focal, generalized, myoclonic types, or status epilepticus, and are not dose-related manifestations. In our case, the possibility of convulsions caused by other drugs or the misuse of drugs was considered. However, we first identified the introduced drugs and excluded the possibility of an accidental misuse of other drugs. Physicians should be aware of the possible occurrence of unpredictable and serious convulsions when using nefopam.

Comparative Study of Brain Protection Effect between Thiopental and Etomidate Using Bispectral Index during Temporary Arterial Occlusion

OBJECTIVE: This study was conducted to compare the effect of etomidate with that of thiopental on brain protection during temporary vessel occlusion, which was measured by burst suppression rate (BSR) with the Bispectral Index (BIS) monitor. METHODS: Temporary parent artery occlusion was performed in forty one patients during cerebral aneurysm surgery. They were randomly assigned to one of two groups. General anesthesia was induced and maintained with 1.5-2.5 vol% sevoflurane and 50% N2O. The pharmacological burst suppression (BS) was induced by a bolus injection of thiopental (5 mg/kg, group T) or etomidate (0.3 mg/kg, group E) according to randomization prior to surgery. After administration of drugs, the hemodynamic variables, the onset time of BS, the numerical values of BIS and BSR were recorded at every minutes. RESULTS: There were no significant differences of the demographics, the BIS numbers and the hemodynamic variables prior to injection of drugs. The durations of burst suppression in group E (11.1+/-6.8 min) were not statistically different from that of group T (11.1+/-5.6 min) and nearly same pattern of burst suppression were shown in both groups. More phenylephrine was required to maintain normal blood pressure in the group T. CONCLUSION: Thiopental and etomidate have same duration and a similar magnitude of burst suppression with conventional doses during temporary arterial occlusion. These findings suggest that additional administration of either drug is needed to ensure the BS when the temporary occlusion time exceed more than 11 minutes. Etomidate can be a safer substitute for thiopental in aneurysm surgery.

Efficacy of Low Dose Barbiturate Coma Therapy for the Patients with Intractable Intracranial Hypertension Using the Bispectral(TM) Index Monitoring

OBJECTIVE: Barbiturate coma therapy (BCT) is a useful method to control increased intracranial pressure (IICP) patients. However, the complications such as hypotension and hypokalemia have caused conditions that stopped BCT early. The complications of low dose BCT with Bispectral(TM) index (BIS) monitoring and those of high dose BCT without BIS monitoring have been compared to evaluate the efficacy of low dose BCT with BIS monitoring. METHODS: We analyzed 39 patients with high dose BCT group (21 patients) and low dose BCT group (18 patients). Because BIS value of 40-60 is general anesthesia score, we have adjusted the target dose of thiopental to maintain the BIS score of 40-60. Therefore, dose of thiopental was kept 1.3 to 2.6 mg/kg/hour during low dose BCT. However, high dose BCT consisted of 5 mg/kg/hour without BIS monitoing. RESULTS: The protocol of BCT was successful in 72.2% and 38.1% of low dose and high dose BCT groups, respectively. The complications such as QT prolongation, hypotension and cardiac arrest have caused conditions that stopped BCT early. Hypokalemia showed the highest incidence rate in complications of both BCT. The descent in potassium level were 0.63 +/- 0.26 in low dose group, and 1.31 +/- 0.48 in high dose group. The treatment durations were 4.89 +/- 1.68 days and 3.38 +/- 1.24 days in low dose BCT and high dose BCT, respectively. CONCLUSION: It was proved that low dose BCT showed less severe complications than high dose BCT. Low dose BCT with BIS monitoring provided enough duration of BCT possible to control ICP.

Development of a Critical Pathway of Barbiturate Coma Therapy in the Management for Severe Brain Damage / 간호행정학회지

PURPOSE: This study is a descriptive research to analyze prognostic factors of barbiturate coma therapy (BCT) for severe brain damage patients, to develop a critical pathway (CP) based on the results of analysis and to examine the effect of its clinical application. METHOD: We analyzed medical records of 76 patients who received BCT for more than three days between January 1999 to July 2005. Based on the results of the analysis, we developed a CP and applied it to 12 people during August-December of 2005. RESULT: By application of BCT CP, the mortality rate decreased from 31.6% to 16.7%. It was found that the period of staying at ICU and total period of hospitalization were shortened by 2.78 (13.9%) days and 16.43 (29.4%) days, respectively. The Glasgow coma scale of the recovery group by CP application was 9.03 (4.64) at 72 hours post of BCT and 14.28 (1.82) at discharge from hospital, and DRS was 6.62 (6.38) points. CONCLUSION: By verifying clinical validity of the suggested CP, we believe that we have obtained visible effects standardizing the treatment pathway of BCT for brain damage patients.

Development of a Critical Pathway of Barbiturate Coma Therapy in the Management for Severe Brain Damage / 간호행정학회지

PURPOSE: This study is a descriptive research to analyze prognostic factors of barbiturate coma therapy (BCT) for severe brain damage patients, to develop a critical pathway (CP) based on the results of analysis and to examine the effect of its clinical application. METHOD: We analyzed medical records of 76 patients who received BCT for more than three days between January 1999 to July 2005. Based on the results of the analysis, we developed a CP and applied it to 12 people during August-December of 2005. RESULT: By application of BCT CP, the mortality rate decreased from 31.6% to 16.7%. It was found that the period of staying at ICU and total period of hospitalization were shortened by 2.78 (13.9%) days and 16.43 (29.4%) days, respectively. The Glasgow coma scale of the recovery group by CP application was 9.03 (4.64) at 72 hours post of BCT and 14.28 (1.82) at discharge from hospital, and DRS was 6.62 (6.38) points. CONCLUSION: By verifying clinical validity of the suggested CP, we believe that we have obtained visible effects standardizing the treatment pathway of BCT for brain damage patients.

Medical managements of intracranial hypertension

Normal intracranial pressure (ICP) is below 10?15 mmHg.It may increase as a result of traumatic brain injury, stroke, neoplasm or other pathologies. When ICP is pathologically elevated it needs to be lowered. Effective management of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate intracranial hypertension.It is important to rule out space occupying lesion that should be surgically removed.Medical managements of intracranial hypertension include maintenance of proper oxygenation and cerebral perfusion pressure and osmotheraphy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical treatment, profound hyperventilation, barbiturate coma or hypothermia should be considered. Steroids are not indicated and maybe harmful in the treatment of intracranial hypertension caused by traumatic brain injury.

The Effect of Barbiturate Coma Therapy for the Patients with Severe Intracranial Hypertension : A 10-Year Experience

OBJECTIVE: Barbiturate coma therapy (BCT) has been known to be an useful method to control increased intracranial pressure (IICP) refractory to medical and surgical treatments. We have used BCT for patients with severe IICP during the past 10 years, and analyzed our results with review of literatures. METHODS: We analyzed 92 semicomatose or comatose patients with Glasgow coma scale (GCS) of 7 or less with severe IICP due to cerebral edema secondary to parenchymal damages irrespective of their causes. Forty patients who had received BCT with ICP monitoring from January 1997 to December 2006 were included in BCT group, and fifty-two patients who had been managed without BCT from January 1991 to December 1995 were divided into control group. We compared outcomes with Glasgow outcome scale (GOS) and survival rate between the two groups. RESULTS: Good outcome (GOS=4 and 5) rates at 3-month after insult were 27.5% and 5.8% in BCT and control group, respectively (p<0.01). One-year survival rates were 35.9% and 12.5% in BCT and control group, respectively (p<0.01). In BCT group, the mean age of good outcome patients (37.1 +/- 14.9) was significantly lower than that of poor outcome patients (48.1 +/- 13.5) (p<0.05). CONCLUSION: With our 10-year experience, we suggest that BCT is an effective treatment method for severe IICP patients for better survival and GOS, especially for younger patients.

Cardiac Arrest due to Severe Hypokalemia during Barbiturate Coma Therapy in a Patient with Severe Acute Head Injury: A case report / 대한마취과학회지

An emergency left frontotemporal craniectomy with direct neck clipping and hematoma removal was performed in a 36-year-old man with a ruptured left middle cerebral artery aneurysm and sylvian hematoma. Because of severe brain swelling postoperatively, we induced barbiturate coma therapy to treat his intractable brain swelling. He had an initial loading dose of sodium thiopental (5 mg/kg) followed by continuous infusion of sodium thiopental (5 mg/kg/hour). The lowest potassium concentration recorded during the barbiturate coma therapy was 1.1 mmol/L; necessitating treatment with cardiac massage, epinephrine, and atropine because of asystole and severe bradycardia. However, he did not recover from cardiac arrest. We present here a case of cardiac arrest due to severe life threatening hypokalemia that occurred during barbiturate coma therapy.

Management of Complex Regional Pain Syndrome Type 1 with Barbiturate Coma Therapy: A case report / 대한통증학회지

Although various treatments for complex regional pain syndrome (CRPS) have been proposed, no well recognized treatment for CRPS has been established. Herein, a case using barbiturate coma therapy for the refractory pain management of a 24-year-old male patient, who suffered from constant stabbing and burning pain, with severe touch allodynia in the left upper extremity following blunt trauma on his forearm is described. Interventional treatments, including permanent spinal cord stimulation and large doses of oral medications, were performed. However, the pain could not be controlled, which lead to frequent emergency room treatment for about 1 month prior to his therapy. He then underwent barbiturate coma therapy due to the uncontrollable pain, with repeated sedation therapy due to his outrageous behavior. His pain became increasingly tolerable and the allodynia was markedly decreased after 5 days of coma therapy.

Successful Hemoperfusion in Acute Phenobarbital Intoxication / 대한신장학회잡지

Phenobarbital is long acting barbiturate with low lipid solubility that act as central nervous system depressants and used as anticonvulsant, sedative, hypnotic drug. In acute severe barbiturate intoxication, through CNS depression, coma, respiratory arrest and hypotension may occur, which are the major causes of mortality. Mortality is 3% for blood levels over 80 mg/mL and the lethal dose in adult is estimated as 6 to 10 g. We report a case of phenobarbital intoxication in a 20 years old female, who was successfully treated by emergency hemoperfusion. She was in semicomatous state and had respiratory difficulty on the day of admission. It was estimated that she intakes 1.6 g of phenobarbital. She was treated with mechanical ventilation, urine alkalization and charcoal administration. Hemoperfusion was attempted to remove rapidly phenobarbital from blood. After hemoperfusion the blood phenobarbital level was decreased from 96 mg/mL to 67 mg/mL. On 2nd hospital day, the blood phenobarbital level was 56 mg/mL and she recovered her self respiration and mentality.

Barbiturate Coma Therapy in Severe and Refractory Vasospasm Following Subarachnoid Hemorrhage

OBJECTIVE: This study is designed to evaluate the therapeutic effects and prognostic factors for barbituate coma therapy(BCT)in severe and refractory vasospasm following subarachnoid hemorrhage. METHODS: Barbiturate coma therapy was used in 18 patients with severe and refractory vasospasm in spite of "3-H therapy" and intra-arterial papaverine infusion. The authors analyzed the clinical parameters including Glasgow Coma Scale(GCS), electroenceplographic finding, and brain computerized tomography(CT) scan findings in relation to outcome at discharge. RESULTS: Among 18 patients, burst suppression pattern could be obtained in 17. In cases with good outcome, the duration elapsed from coma to drowsiness after BCT was 14.09+/-5.82 days and GCS score at this time was significant in the prediction of final outcome(p<0.05). Patients with ideal burst suppression pattern attainable more than 24 to 48 hours showed good outcome in 81.8%(p<0.05). The group that showed focal low density in the brain CT scan taken before BCT fared better prognosis compared with that of multifocal or diffuse low density(p<0.05), and patients with resolution of perimesencephalic cistern effacement on follow-up brain CT scan taken 48 hours after BCT showed better prognosis(p<0.05). Overall, 72.2% showed improvement of GCS score by 2 or more, and good outcome was noted in 50%. CONCLUSION: The barbiturate coma therapy seems to have a beneficial therapeutic effect on severe and refractory vasospasm and can be considered as a useful therapeutic modality.

Rebounded Response in Propofol Coma Therapy / 대한마취과학회지

Barbiturate has been used for the therapy of increased intracranial pressure (ICP) patients. However, it has some serious side effects such as rebound response or convulsion. According to recent reports, propofol can be used for coma therapy and the therapeutic result has been satisfactory. We used propofol instead of barbiturate in coma therapy and experienced a case of rebound response. On admission day, a 20-year-old female patient received an endovascular embolization for an arteriovenous malformation (AVM) in the left occipital lobe. The next day, she went into a coma and the brain CT showed a massive intracerebral hematoma at the AVM site. The patient was transferred to the operating room for decompressive surgery. At the end of the surgery, the brain edema did not subside. The patient was infused with propofol (4 mg/kg/h) after the surgery for propofol coma therapy. During the 6 day propofol therapy, ICP was effectively controlled under 20 mmHg. After completion of the propofol coma therapy, the patient was revived enough to verbally obey. 16 hours later, ICP increased to more than 30 mmHg and the patient was reinfused with propofol. We experienced a rebound response in propofol coma therapy similar to that in barbiturate coma therapy.

Influence of the central benzodiazepinergic system on peripheral cardiovascular regulation

Diazepam is known to have cardiovascular depressive effects through a combined action on benzodiazepinergic receptor and the GABA receptor-chloride ion channel complex. Moreover, it is known that barbiturates also have some cardiovascular regulatory effects mediated by the central GABAergic system. Therefore, this study was undertaken to delineate the regulatory actions and interactions of these systems by measuring the responses of the cardiovascular system and renal nerve activity to muscimol, diazepam and pentobarbital, administered intracerebroventricularly in rabbits. When muscimol (0.03~-0.3 microgram/kg), diazepam (10~100 microgram/kg) and pentobarbital (1-10 microgram/kg) were injected into the lateral ventricle of the rabbit brain, there were similar dose-dependent decreases in blood pressure (BP) and renal nerve activity (RNA). The relative potency of the three drugs in decreasing BP and RNA was muscimol > pentobarbital >diazepam. Muscimol and pentobarbital also decreased the heart rate in a dose-dependent manner; however, diazepam produced a trivial, dose-independent decrease in heart rate. Diazepam (30 microgram/kg) pentobarbital (3 microgram/kg) did not. Bicuculline (0.5 microgram/kg), a GABAergic receptor blocker, significantly augmented the effect of muscimol (0.1 microgram/kg) in decreasing blood pressure and renal nerve activity, but of pentobarbital in decreasing BP and RNA, either alone or with muscimol. We inferred that the central benzodiazepinergic and barbiturate systems help regulate peripheral cardiovascular function by modulating the GABAergic system, which adjusts the output of the vasomotor center and hence controls peripheral sympathetic tone. Benzodiazepines more readily modulate the GABAergic system than barbiturates.

The Effect of Barbiturate in Brain Protection under Mild Hypothermia During Temporary Vessel Occlusion in Aneurysm Surgery

Temporary vessel occulusion is a useful technique which facilitates aneurysmal dissection and clipping, and reduces the risk of intraoperative aneurysal rupture; It may, however, result in postoperative stroke, and many authors have therefore used various agents for brain protection. Among these, barbiturate is well known. This study was undertaken to retrospectively review the effect of barbiturate on brain protection during short periods of ischemia. It involved patients with 146 anterior circulation aneurysms, who were divided into two groups: 43 who received intraoperative barbiturate burst suppression with sodium thiopental during temporary vessel occlusion and the remaining 103, who did not. Doses of thiopental 5mg/kg, usually singly or occasionally repeated at 10-mimute interval, were administered. All patients underwent general anesthesia using volatile isoflurane; mild hypothermia(32-34degreesC), mild hypocarbia(30-35mmHg), and normotension of 110-130mmHg were noted prior to permanent clipping, and mild hypertension(130-150mmHg) after clipping. In some cases, intraoperative scalp electroencep-halography was monitored. Clinical, radiological, and overall infarction were assessed postoperatively, and statistical analysis was perfomed. With regard to Hunt-Hess grades, number of episodes of occlusion, duration of temporary clip application lasting less than 13 minutes, and period of post-subarachnoid hemorrhage, no significant differences were seen between the two groups. Patients in whom barbiturate burst was suppressed showed a 4-hours delay in mean anesthetic recovery time, and after thiopental sodium was injected intravenously, systolic and mean arterial pressure(MAP), averaging 10-20mmHg, were lowered than in those without this suppression. In conclusion, we had found that under mild hypothermic anesthesia involving less than 13 minutes of temporary vessel occlusion, protection of the brain by barbiturate was not beneficial.

Aneurysms of the Basilar Artery Treated with Circulatory Arrest , Hypothermia and Barbiturate Cerebral Protection - 2 cases - / 대한마취과학회지

Surgical and anesthetic management in patients with complex vascular lesions is often challenging. Cardiopulmonary bypass followed by total circulatory arrest, deep hypothermia and barbiturate cerebral protection are efficacious adjuncts in the surgical treatment of giant basilar artery aneurysm. These techniques were utillized in two large basilar artery aneurysm patients with good results, and the surgical and anesthetic considerations are reviewed.

A Case of Giant Intracranial Aneurysm Treated with Total Circulatory Arrest, Hypothermia, and Barbiturate Cerebral Protection

We are reporting a case of giant intracranial aneurysm operated under circulatory arrest. The patient was a 36-year-old woman with right hemiparesis and dysarthria. Brain MRI and angiographgy disclosed a partially thrombosed, dumbbell-shaped giant aneurysm involving the left distal ICA and M1 portion of the MCA. The patient was treated with direct clipping under total circulatory arrest, hypothermia, and barbiturate cerebral protection. The clipping could be done more easily than with conventional methodology because the aneurysm was softened. But the patient didn't recover due to postoperative intracerebral hemorrhage and possible embolic infarct.

Therapeutic Barbiturate Coma in Uncontrolled Intracranial Hypertension : Management of Patients and Effect on Outcome

In spite of high-dose, hyperventilation, hyperosmolar agents, appropriate surgical evacuation, and cerebrospinal fluid when possible, uncontrolled intracranial hypertension, which was defined as occurring when intracranial pressure(ICP) exceeded 25 mmHg for 2 hours or more, occurred in 8 patients. Persistent elevated ICP occurred in 4 patient with acute subdural hematoma and brain contusion, in 2 patients with aneurysm and brain infarction, in 1 patient with hypertensive intracerebral hematoma, and in 1 patient with meningioma. All of these patients received intravenous barbiturate to control the ICP. The initial thiopental loading dose(10mg/kg) effectively reduced the ICP in 5 patients(62.5%). In those patients responding to the initial loading dose, four have survived, and one died due to pulmonary complication. None of three nonresponders to barbiturate survived. Two of the survivors have returned to a productive life, and two ramain moderately disabled. The favorable outcome in this series suggests that early aggresive treatment of intracranial hypertension with barbiturate and careful attention to medical complications can improve the outcome in patients with uncontrolled intracranial hypertension, with barbiturate and careful attention to medical complications can improve the outcome in patients with uncontrolled intracranial hypertension, especially in postoperative state. A broader investigation of the clinical application of barbiturates in indicated.