Treatment Of Refractory Intracranial Hypertension Research Articles

Pentobarbital Coma With Therapeutic Hypothermia for Treatment of Refractory Intracranial Hypertension in Traumatic Brain Injury Patients: A Single Institution Experience.

IntroductionTraumatic brain injury (TBI) results in primary and secondary brain injuries. Secondary brain injury can lead to cerebral edema resulting in increased intracranial pressure (ICP) secondary to the rigid encasement of the skull. Increased ICP leads to decreased cerebral perfusion pressure which leads to cerebral ischemia. Refractory intracranial hypertension (RICH) occurs when ICP remains elevated despite first-tier therapies such as head elevation, straightening of the neck, analgesia, sedation, paralytics, cerebrospinal fluid (CSF) drainage, mannitol and/or hypertonic saline administration. If unresponsive to these measures, second-tier therapies such as hypothermia, barbiturate infusion, and/or surgery are employed.MethodsThis was a retrospective review of patients admitted at Arrowhead Regional Medical Center from 2008 to 2019 for severe TBI who developed RICH requiring placement into a pentobarbital-induced coma with therapeutic hypothermia. Primary endpoints included mortality, good recovery which was designated at Glasgow outcome scale (GOS) of 4 or 5, and improvement in ICP (goal is <20 mmHg). Secondary endpoints included complications, length of intensive care unit (ICU) stay, length of hospital stay, length of pentobarbital coma, length of hypothermia, need for vasopressors, and decompressive surgery versus no decompressive surgery.ResultsOur study included 18 patients placed in pentobarbital coma with hypothermia for RICH. The overall mortality rate in our study was 50%; with 60% mortality in pentobarbital/hypothermia only group, and 46% mortality in surgery plus pentobarbital/hypothermia group. Maximum ICP prior to pentobarbital/hypothermia was significantly lower in patients who had a prior decompressive craniectomy than in patients who were placed into pentobarbital/hypothermia protocol first (28.3 vs 35.4, p<0.0238). ICP was significantly reduced at 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after pentobarbital and hypothermia treatment. Initial ICP and maximum ICP prior to pentobarbital/hypothermia was significantly correlated with mortality (p=0.022 and p=0.026). Patients with an ICP>25 mmHg prior to pentobarbital/hypothermia initiation had an increased risk of mortality (p=0.0455). There was no statistically significant difference in mean ICP after 24 hours after pentobarbital/hypothermia protocol in survivors vs non-survivors. Increased time to reach 33°C was associated with increased mortality (r=0.47, p=0.047); with a 10.5-fold increase in mortality for >7 hours (OR 10.5, p=0.039).ConclusionProlonged cooling time >7 hours was associated with a 10.5-fold increase in mortality and ICP>25 mmHg prior to initiation of pentobarbital and hypothermia is suggestive of a poor response to treatment. We recommend patients with severe TBI who develop RICH should first undergo a 12 x 15 cm decompressive hemicraniectomy because they have better survival and are more likely to have ICP <25 mmHg as the highest elevation of ICP if the ICP were to become and stay elevated again. Pentobarbital and hypothermia should be initiated if the ICP becomes elevated and sustained above 20 mmHg with a prior decompressive hemicraniectomy and refractory to other medical therapies. However, our data suggests that patients are unlikely to survive if there ICP does not decrease to less than 15mmHg at 8 and 12 hours after pentobarbital/hypothermia and remain less than 20 mmHg within first 48 hours.

Management of Australian Patients with Severe Traumatic Brain Injury: Are Potentially Harmful Treatments Still Used?

Clinical trials have shown that intravenous albumin and decompressive craniectomy to treat early refractory intracranial hypertension can cause harm in patients with severe traumatic brain injury (TBI). The extent to which these treatments remain in use is unknown. We conducted a multi-center retrospective cohort study of adult patients with severe TBI admitted to five neurotrauma centers across Australia between April 2013 and March 2015. Patients were identified from local trauma and intensive care unit (ICU) registries and followed until hospital discharge. Main outcome measures were the administration of intravenous albumin, and decompressive craniectomy for intracranial hypertension. Analyses were predominantly descriptive. There were 303 patients with severe TBI, of whom a minority received albumin (6.9%) or underwent early decompressive craniectomy for treatment of refractory intracranial hypertension complicating diffuse TBI (2.3%). The median (intequartile range [IQR]) age was 35 (24, 58), and most injuries were caused by road traffic accidents (57.4%) or falls (25.1%). Overall, 34.3% of patients died while in the hospital and the remainder were discharged to rehabilitation (44.6%), other health care facilities (4.6%), or home (16.5%). There were no patient characteristics significantly associated with use of albumin or craniectomy. Intravenous albumin and craniectomy for treatment of intracranial hypertension were used infrequently in Australian neurotrauma centers, indicating alignment between best available evidence and practice.

Internal Cranial Expansion for Treatment of Refractory Intracranial Hypertension in an Adult Population

Internal Cranial Expansion for Treatment of Refractory Intracranial Hypertension in an Adult Population

Iatrogenic Propylene Glycol Intoxication Due to High-Dose Pentobarbital for Refractory Intracranial Hypertension: A Case Report

Propylene glycol is a rarely reported toxicity from high-dose administration of certain intravenous drugs, including lorazepam and pentobarbital. We present a case of iatrogenic propylene glycol toxicity secondary to a high-dose pentobarbital infusion for the treatment of refractory intracranial hypertension due to cerebral venous sinus thrombosis. The patient developed metabolic acidosis and acute kidney failure secondary to propylene glycol toxicity. After initiation of continuous renal replacement therapy, the patient’s acute renal failure and lactic acidosis resolved. Using the Naranjo scale, this case received a score of 5, defining it as a “probable” adverse drug event. In patients who develop lactic acidosis and acute renal failure after initiation of high-dose pentobarbital, propylene glycol toxicity should be higher up in the differential diagnosis. Monitoring the serum osmolality while on pentobarbital could help provide valuable information to prevent iatrogenic propylene glycol toxicity.

Lumbar drainage for the treatment of refractory intracranial hypertension in HIV-negative cryptococcal meningitis.

Aim: This study aims to evaluate lumbar drainage (LD) for controlling refractory intracranial hypertension among non-HIV cryptococcal meningitis patients. Patients & methods: A case-control study was designed to compare LD (case) with repeated lumbar puncture (control). Results: Both LD and repeated lumbar puncture can efficiently control refractory intracranial hypertension. LD group showed better clinical symptomremission, such as lower rate of headache, vision disorders, signs of meningeal irritation and conscious disturbance, than control group. LD group was reported with higher intracranial pressure reduction (173.75±17.72 mmH2O) than those among control group (113.50±14.94 mmH2O; p <0.05). Conclusion: LD is an effective and safe alternative to control refractory intracranial hypertension in HIV-negative cryptococcal meningitis patients.

Características do Hematoma Epidural Contralateral após Craniectomia Descompressiva para Tratamento de Trauma Cranioencefálico Grave. Revisão Sistemática

Introdução: A craniectomia descompressiva é considerada como o método cirúrgico mais utilizado no tratamento da hipertensão intracraniana refratária decorrente da injúria cerebral grave. Apesar de ser descrita como método resolutivo quando bem indicado, pode contar com severas complicações precoces, destacando-se dentre elas o hematoma epidural contralateral. Objetivos: Descrever os principais achados clínicos e tomográficos de pacientes que apresentaram hematoma epidural contralateral após a realização da craniectomia descompressiva para tratamento do trauma cranioencefálico grave. Metodologia: Trata-se de uma revisão sistemática de literatura, sem metanálise, realizada pelas bases de dados Pubmed e Scielo. Resultados: Foram encontrados sessenta e sete pacientes acometidos por hematoma epidural contralateral após a realização da craniectomia descompressiva. A suspeição para a formação do novo sangramento foi observada pela anormalidade pupilar (22,3%) e aumento da pressão intracraniana (18%) no pós-operatório, pelo inchaço cerebral no momento da primeira cirurgia (22,3%) ou revelado pela tomografia computadorizada de rotina (26,8%). Pelo menos 86,36% dos pacientes apresentaram fratura óssea contralateral ao hematoma inicial. Conclusão: O hematoma epidural contralateral tem uma incidência de 5,2%. A fratura óssea contralateral ao hematoma inicial se destaca como principal característica para o desenvolvimento de hematoma epidural contralateral. O edema cerebral intra-operatório inexplicável ou a presença de anormalidades pupilares no pós-operatório, se destacam como bom indicador do desenvolvimento do hematoma contralateral. Em contrapartida, a deterioração neurológica e a presença de coagulopatias não é uma característica confiável de hematoma epidural contralateral após craniectomia descompressiva.

Hypothermia in the treatment of refractory intracranial hypertension in patients with severe SAH, cases associated with secondary vasospasms

Subarachnoid hemorrhage (SAH) is a severe disease in which 10% of patients may present sudden death before arriving at the hospital. Patients are exposed to a high risk of secondary complications including vasospasm. For refractory vasospasm and essentially for ICP control, hypothermia may be employed for the treatment.We aimed to evaluate the influence of therapeutic hypothermia in mortality rates of patients with severe SAH with high intracranial pressure despite best clinical treatment. Temperatures were reduced using mattress for a target temperature of 33-35o C. Five patients were included. Two patients were admitted with a Hunt-Hess scale grade of 2, two of 3 and one of 4. The mean length of therapeutic hypothermia was 7.2 days. Two patients survived with a Rankin scale of 0, and three died. In our observational study we observed a 180 days mortality rate of 40% that increased to 60% in six month analysis. Recent trials describe a mortality rate of 90% in patients with SAH and refractory ICH11. We believe hypothermia may be the best method to be employed in this clinical situation.

Dexmedetomidine for Refractory Intracranial Hypertension.

Dexmedetomidine (DEX) is a selective α2 adrenergic agonist that is commonly used for sedation in the intensive care unit (ICU). The role of DEX for adjunctive treatment of refractory intracranial hypertension is poorly defined. The primary objective of this study was to determine the effect of DEX on the need for rescue therapy (ie, hyperosmolar boluses, extraventricular drain [EVD] drainages) for refractory intracranial hypertension. Secondary objectives included the number of intracranial pressure (ICP) excursions, bradycardic, hypotensive, and compromised cerebral perfusion pressure episodes. This retrospective cohort study evaluated patients admitted to the neurosurgical ICU from August 1, 2009, to July 29, 2015, and who received DEX for refractory intracranial hypertension. The objectives were compared between the 2 time periods-before (pre-DEX) and during therapy (DEX). Twenty-three patients with 26 episodes of refractory intracranial hypertension met the inclusion criteria. The number of hyperosmolar boluses was decreased after DEX therapy was initiated. Mannitol boluses required were statistically reduced (1 vs 0.5, P = .03); however, reduction in hypertonic boluses was not statistically significant (1.3 vs 0.9, P = .2). The mean number of EVD drainages per 24 hours was not significantly different between the time periods (15.7 vs 14.0, P = .35). The rate of ICP excursions did not differ between the 2 groups (24.3 vs 22.5, P = .62). When compared to pre-DEX data, there was no difference in the median number of hypotensive (0 vs 0), bradycardic (0 vs 0), or compromised cerebral perfusion pressure episodes (0.5 vs 1.0). Dexmedetomidine may avoid increases in the need for rescue therapy when used as an adjunctive treatment of refractory intracranial hypertension without compromising hemodynamics.

Effective treatment of refractory intracranial hypertension after traumatic brain injury with repeated boluses of 14.6% hypertonic saline

Normal intracranial pressure (ICP) and cerebral perfusion pressure (CPP) have been identified as favorable prognostic factors in the outcome of patients with traumatic brain injuries (TBIs). Osmotic diuretics and hypertonic saline (HTS) are commonly used to treat elevated ICP in patients with TBI; however, sustained effects of repeated high-concentration HTS boluses for severely refractory ICP elevation have not been studied. The authors' goal in this study was to determine whether repeated 14.6% HTS boluses were efficacious in treating severely refractory intracranial hypertension in patients with TBI. In a prospective cohort study in a neurocritical care unit, adult TBI patients with sustained ICP > 30 mm Hg for more than 30 minutes after exhaustive medical and/or surgical therapy received repeated 15-minute boluses of 14.6% HTS over 12 hours through central venous access. Response to treatment was evaluated in 11 patients. Within 5 minutes of bolus administration, mean ICP decreased from 40 to 33 mm Hg (30% reduction, p < 0.05). Intracranial pressure-lowering effects were sustained for 12 hours (41% reduction, p < 0.05) with multiple boluses (mean number of boluses 7 ± 5.5). The mean CPP increased 22% and 32% from baseline at 15 and 30 minutes, respectively (p < 0.05). The mean serum sodium level (SNa) at baseline was 155 ± 7.1 mEq/L, and after multiple boluses of 14.6% HTS, S(Na) at 12 hours was 154 ± 7.1 mEq/L. The mean heart rate, systolic blood pressure, blood urea nitrogen, and creatinine demonstrated no significant change throughout the study. The subset of TBI patients with intracranial hypertension that is completely refractory to all other medical therapies can be treated effectively and safely with repeated boluses of 14.6% HTS rather than a one-time dose.

Internal cranial expansion surgery for the treatment of refractory idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH) may be refractory to available medical and surgical therapies. Patients with this condition may suffer from intractable headaches, experience visual deterioration, or have other symptoms related to elevated intracranial pressure. Internal cranial expansion (ICE) is a novel surgical procedure that the authors have developed for the treatment of patients with this condition. Here, they describe ICE and present their initial experience in using this surgical procedure for the treatment of patients with refractory IIH. The authors conducted a retrospective review of 10 consecutive patients who underwent ICE for the treatment of IIH during a 5-year period. Preoperative and postoperative clinical parameters including patient symptoms, presence of papilledema, and available ICP or CSF opening pressures were compared. Procedural details and complications were noted. Intracranial volume increases were calculated using available pre- and postoperative CT scans. Follow-up for the 10 patients in this series ranged from 1 to 39.6 months (mean 15.5 months). Technically successful ICE was performed in all patients within the cohort. Surgical complications included a single postoperative seizure in one patient and a sagittal sinus tear with no clinical sequelae in another patient. At the time of last follow-up, 7 (70%) of 10 patients were either symptomatically improved or asymptomatic. Six (67%) of 9 patients with preoperative headaches had reduction or resolution of this symptom, and all patients (4 of 4) with preoperative papilledema had a reduction in or complete resolution of this sign. Postoperative ICP or CSF opening pressures were normal in all patients (4 of 4) tested. Postoperative intracranial volume expansion ranged between 3.8% and 12%. Internal cranial expansion is a safe and effective surgery for the treatment of patients with refractory IIH. This surgery expands the intracranial volume and thus promotes ICP normalization, which may lead to the reduction or complete resolution of the signs and symptoms of IIH. Internal cranial expansion may be used as part of a multidisciplinary management approach in the treatment of refractory IIH.

Treatment of refractory intracranial hypertension with 23.4% saline in children with severe traumatic brain injury

The safety and efficacy of osmotic therapy with mannitol and 3% saline in the pediatric head-injured population has been widely reported; the use of 23.4% saline in children for the treatment of refractory intracranial hypertension has not. The clinical and physiologic responses of multiple 23.4% saline boluses in two children with severe traumatic brain injury (TBI) are presented. No complications were associated with the use of 23.4% saline in either patient.

Chapter 3. Indications for intracranial pressure monitoring

Chapter 3. Indications for intracranial pressure monitoring

Chapter 10. Cerebrospinal fluid drainage

Chapter 10. Cerebrospinal fluid drainage

Comment gérer l’hypertension intracrânienne réfractaire ?

Intracranial hypertension is one of the major causes of secondary injury in traumatic brain injury leading to a significant burden of morbidity and mortality. We here present a review of available therapies for the treatment of refractory intracranial hypertension that is defined as an intracranial hypertension that does not respond to the firstline therapies. Second-line therapies that are available for the treatment of refractory intracranial hypertension include mild induced hypothermia, inotropes, and vasopressors for the control of cerebral perfusion pressure, transient hyperventilation, barbiturates, and decompressive craniectomy. Apart from decompressive craniectomy, these therapies are supported by the last guidelines published by the Brain Trauma Foundation (BTF). However, the level of evidence supporting them is low to moderate. This is probably partly explained by the fact that traumatic brain injury is extremely heterogeneous and requires multimodal and individualised care, which makes randomised clinical trials difficult to set up. On-going studies like those conducted on induced hypothermia (EUROTHERM3235) and on decompressive craniectomy (RESCUEicp) may lead to new perspectives for the management of patients suffering from refractory intracranial hypertension.

Decompressive Craniectomy for Elderly Patients with Traumatic Brain Injury: It's Probably not Worth the While

Decompressive craniectomy (DC) has been regarded as an ultima ratio measure in the treatment of refractory intracranial hypertension after brain injury. Most discussion about its benefits is based on studies performed in patients who are <65 years of age. The aim of this study was to identify patients aged ≥66 years who underwent DC after traumatic brain injury (TBI), in order to assess patient outcome and to correlate the values of potential predictors of survival on prognosis. From January 2002 to December 2009, 44 patients aged ≥66 underwent DC (follow-up, 12-102 months). Potential predictors of outcome were analyzed, including age, post-resuscitation Glasgow Coma Scale (GCS) score, presence of mass lesion, Simplified Acute Physiology Score (SAPS) II, Injury Severity Score (ISS), and timing of surgical decompression. Mortality was 48% at discharge from the intensive care unit (ICU), 57% at hospital discharge, and 77% at 1-year follow-up and at last follow-up. A bad outcome Glasgow Outcome Scale Dead-Vegetative State-Severely Disabled (GOS D-VS-SD) was observed in 36/44 patients both at hospital discharge and at 1-year follow-up. Mean SAPS II was 45.2 for patients who survived and 57.3 for patients who had died (p=0.0022). Patients who survived had a higher mean post-resuscitation GCS score (p=0.02). Logistical regression analysis indicated post-resuscitation GCS score as the only independent predictive factor for outcome. None of the 22 patients with a post-resuscitation GCS score of 3-5 had a good outcome, 2/10 (20%) patients with a post-resuscitation GCS score of 6-8 and 6/12 patients (50%) with a post-resuscitation GCS score ≥9 had a good outcome.

Hypertonic Saline Reduces Intracranial Hypertension in the Presence of High Serum and Cerebrospinal Fluid Osmolalities

Osmotherapy has been the cornerstone in the management of patients with elevated intracranial pressure (ICP) following traumatic brain injury (TBI). Several studies have demonstrated that hypertonic saline (HTS) is a safe and effective osmotherapy agent. This study evaluated the effectiveness of HTS in reducing intracranial hypertension in the presence of a wide range of serum and cerebrospinal fluid (CSF) osmolalities. Forty-two doses of 23.4% saline boluses for treatment of refractory intracranial hypertension were reviewed retrospectively. Thirty milliliters of 23.4% NaCl was infused over 15min for intracranial hypertension, defined as ICP>20mmHg. The CSF and serum osmolalities from frozen stored samples were measured with an osmometer. The values of serum sodium, hourly ICP, blood urea nitrogen (BUN), and creatinine were obtained directly from the medical records. The serum and CSF osmolalities correlated very closely to serum sodium (r>0.9, P<0.0001). The reduction in ICP from the baseline (measured from either the mean ICP or the lowest ICP measurement in the first 6h after bolus HTS treatment) was statistically significant regardless of serum osmolality. The mean reduction from baseline to follow-up values was 8.8mm Hg (P<0.0001). The decrease in ICP was as evident with serum osmolalities>320 as it was at≤320. This study demonstrates that 23.4% HTS bolus is effective for the reduction of elevated ICP in patients with severe TBI even in the presence of high serum and CSF osmolalities.

Cerebral hemodynamic and metabolic effects of propofol or thiopental in the treatment of refractory intracranial hypertension in patients with severe traumatic brain injury: A preliminary study

Cerebral hemodynamic and metabolic effects of propofol or thiopental in the treatment of refractory intracranial hypertension in patients with severe traumatic brain injury: A preliminary study

Treating intracranial hypertension in traumatic brain injury: keep it cool!

Stocchetti et al. [1] have reported their experience with currently available “second tier” therapeutic options for the treatment of refractory intracranial hypertension in patients with traumatic brain injury (TBI) in three Italian neurotrauma centres. The authors discuss three options to control intracranial pressure: profound hyperventilation, barbiturate coma and decompressive craniectomy. These options were used alone or in combination. We were surprised that fever management and mild therapeutic hypothermia were not discussed or even mentioned (other than as a potential source of complications) in this article. Various research groups (including one of the centres involved in the present study) have reported that development of fever following TBI is closely linked to intracranial hypertension [2–5]; this would suggest that fever management should be one of the first steps in controlling intracranial hypertension, but this is not mentioned in the article of Stocchetti et al. Further, it has been conclusively demonstrated (in 14 studies enrolling >1,500 patients) that ICP can be significantly decreased by induction of mild hypothermia [5–10]. Moreover, although the results from studies using hypothermia to improve outcome following severe TBI have been conflicting, the preponderance of evidence strongly suggests that prolonged (3–5 days) cooling can significantly improve neurological outcome in patients with intracranial hypertension [5–10]. None of the therapeutic options discussed by Stocchetti et al. has so far been shown to improve neurological outcome; studies using barbiturate coma [11–13] or hyperventilation [14–15] in patients with refractory intracranial hypertension reported decreases in ICP but no benefits in outcome. Decompressive craniotomy has shown promise in one small study in 27 paediatric patients [16], but has not yet been well studied in adults [17]. Two RCTs addressing this issue are currently in process [18–19]. Hypothermia does not decrease cerebral blood flow without reducing metabolism and oxygen demand, as is the case with hyperventilation [20], and, when used judiciously, tends to cause no hypotension and less myocardial dysfunction than barbiturates. The evidence regarding improved neurological outcome in TBI associated with hypothermia can certainly be debated; but the evidence is (at the very least!) as strong and as favourable as for barbiturates and hyperventilation. Therefore, induced hypothermia should be regarded as one of the “second tier” therapies in refractory intracranial hypertension, and as such deserves to be mentioned as a feasible option in the otherwise excellent discussion by Stocchetti et al.

Lumbar drainage as treatment of refractory intracranial hypertension in bacterial meningitis

Lumbar drainage as treatment of refractory intracranial hypertension in bacterial meningitis

Efficacy of different hypertonic solutes in the treatment of refractory intracranial hypertension in severe head injury patients: A comparative study of 2ml/kg 7.5% hypertonic saline and 2ml/kg 20% mannitol

A prospective, randomized study to evaluate the clinical benefit of increasing the osmotic load of the hypertonic solution administered for the treatment of refractory intracranial hypertension episodes in patients with severe head injury. 25 patients with severe head injury and persistent coma, admitted in a Neurocritical Care Unit of a Tertiary Care Hospital, who required infusions of osmotic agents to treat episodes of intracranial hypertension resistant to well defined standard modes of therapy were randomly allocated to one of the two groups to receive isovolume infusions of either 7.5% hypertonic saline solution; HS [2400 mOsm/kg H2O] or 20% mannitol [1160 mOsm/kg of H2O] given 2ml/kg of either solution, i.e. 331.5 +/− 35.4 mOsm of hypertonic saline or 174.2 +/− 18 mOsm of mannitol per infusion. The variables recorded in the study were the duration and number of episodes of intracranial hypertension per day during the study period, which was stopped after the last episode of intracranial hypertension was recorded from intracranial pressure recording or after the allocated treatment failure. Patients of HS group were monitored for 7 +/− 6 days and those in the mannitol group for 8 +/− 5 days [p=NS]. The rate of failure for each treatment was also evaluated which was defined as the persistence of intracranial hypertension despite the two successive infusions of the same osmotic agent. The mean number of osmotic solute infusions was 3.4 +/− 4.5 in the HS group and 3.8 +/− 5.1 in mannitol group p=NS]. The mean number [7.1+/-2.9 vs. 14.6+/−3.4] of episodes of intracranial hypertension per day and the duration of such episode [62.6+/−28.1 vs. 93.4+/−37.2 min] was also significantly lower in the HS group [p<0.05]. The numbers of treatment failures were significantly lower in HS group: 1 out of 14 patients vs. 6 out of 11 patients [p<0.01]. In this study we have found that in patients with severe head injury requiring treatment with hypertonic solute for refractory intracranial hypertension, 2ml/kg body weight of 7.5% HS [356 +/− 14 mOsm] was more effective than giving 2ml/kg 20% mannitol [178 +/− 11mOsm]. Within the limitations of present study, the collected data suggest that giving 2ml/kg HS solution is an effective and safe initial treatment for intracranial hypertension episodes in head injury patients when there is indication of osmotherapy.