Increase In Cerebral Perfusion Pressure Research Articles

Is hypertonic saline an effective alternative to mannitol in the treatment of TBI in adult and pediatric patients? A systematic review and meta-analysis

Aim: This meta-analysis and systematic review aims to investigate and compare the efficacy of mannitol and hypertonic saline in treating patients who have suffered from traumatic brain injury (TBI). Methods: We reviewed publications from the Medline database, Web of Science, and Google Scholar from inception to 13 October 2022 with only English-based literature. The risk of bias from included Randomized controlled trial (RCT) s was assessed using the Cochrane Collaboration's Tool. Newcastle-Ottawa Scale was employed to assess the included cohort\'s quality. The main outcomes of this review were treatment failure, mortality, intracranial pressure (ICP) reduction, and Cerebral Perfusion Pressure (CPP) increment. All the statistical analyses were performed using the Review Manager 5.4.1. A random-effects model was used to pool the studies when heterogeneity was seen, and the results were reported in the odds ratios (OR) and mean differences (MD) and the corresponding 95% confidence intervals. Results: The results of the statistical study found that there was a significantly lower treatment failure rate [OR = 1.80 (1.26, 2.57); p = 0.001; I 2 = 74%], the lower mortality rate [OR = 2.17 (1.26, 3.73); p = 0.005; I 2 = 0%], a greater increase in CPP [MD = -1.28 (-2.50, -0.05); p = 0.04; I 2 = 0%] associated with hypertonic saline treatment as compared to mannitol treatment. However, concerning ICP decrease, there was no significant difference between the two treatment options [MD = 1.86 (-0.64, 4.36); p = 0.14; I 2 = 70%]. Conclusions: Quantitative and qualitative analysis of trials and observational studies comparing the efficacy of hypertonic saline and mannitol demonstrates that hypertonic saline is a preferable treatment option with greater effectiveness and safety than mannitol in managing patients with TBI.

Ketamine Boluses Are Associated with a Reduction in Intracranial Pressure and an Increase in Cerebral Perfusion Pressure: A Retrospective Observational Study of Patients with Severe Traumatic Brain Injury.

Background Increased intracranial pressure (ICP) and hypotension have long been shown to lead to worse outcomes in the severe traumatic brain injury (TBI) population. Adequate sedation is a fundamental principle in TBI care, and ketamine is an attractive option for sedation since it does not commonly cause systemic hypotension, whereas most other sedative medications do. We evaluated the effects of ketamine boluses on both ICP and cerebral perfusion pressure (CPP) in patients with severe TBI and refractory ICP. Methods We conducted a retrospective review of all patients admitted to the neurointensive care unit at a single tertiary referral center who had a severe traumatic brain injury with indwelling intracranial pressure monitors. We identified those patients with refractory intracranial pressure who received boluses of ketamine. We defined refractory as any sustained ICP greater than 20 mmHg after the patient was adequately sedated, serum Na was at goal, and CO2 was maintained between 35 and 40 mmHg. The primary outcome was a reduction in ICP with a subsequent increase in CPP. Results The patient cohort consisted of 44 patients with a median age of 30 years and a median presenting Glasgow Coma Scale (GCS) of 5. The median reduction in ICP after administration of a ketamine bolus was −3.5 mmHg (IQR −9 to +1), and the postketamine ICP was significantly different from baseline (p < 0.001). Ketamine boluses led to an increase in CPP by 2 mmHg (IQR −5 to +12), which was also significantly different from baseline (p < 0.001). Conclusion In this single-institution study of patients with severe traumatic brain injury, ketamine boluses were associated with a reduction in ICP and an increase in CPP. This was a retrospective review of 43 patients and is therefore limited in nature, but further randomized controlled trials should be performed to confirm the findings.

Differential Hemodynamic Response of Pial Arterioles Contributes to a Quadriphasic Cerebral Autoregulation Physiology.

BackgroundCerebrovascular autoregulation (CA) regulates cerebral vascular tone to maintain near‐constant cerebral blood flow during fluctuations in cerebral perfusion pressure (CPP). Preclinical and clinical research has challenged the classic triphasic pressure‐flow relationship, leaving the normal pressure‐flow relationship unclear.Methods and ResultsWe used in vivo imaging of the hemodynamic response in pial arterioles to study CA in a porcine closed cranial window model during nonpharmacological blood pressure manipulation. Red blood cell flux was determined in 52 pial arterioles during 10 hypotension and 10 hypertension experiments to describe the pressure‐flow relationship. We found a quadriphasic pressure‐flow relationship with 4 distinct physiological phases. Smaller arterioles demonstrated greater vasodilation during low CPP when compared with large arterioles (P<0.01), whereas vasoconstrictive capacity during high CPP was not significantly different between arterioles (P>0.9). The upper limit of CA was defined by 2 breakpoints. Increases in CPP lead to a point of maximal vasoconstriction of the smallest pial arterioles (upper limit of autoregulation [ULA] 1). Beyond ULA1, only larger arterioles maintain a limited additional vasoconstrictive capacity, extending the buffer for high CPP. Beyond ULA2, vasoconstrictive capacity is exhausted, and all pial arterioles passively dilate. There was substantial intersubject variability, with ranges of 29.2, 47.3, and 50.9 mm Hg for the lower limit, ULA1, and ULA2, respectively.ConclusionsWe provide new insights into the quadriphasic physiology of CA, differentiating between truly active CA and an extended capacity to buffer increased CPP with progressive failure of CA. In this experimental model, the limits of CA widely varied between subjects.

Optimal Cerebral Perfusion Pressure Guided by Brain Oxygen Pressure Measurement.

Background: Although increasing cerebral perfusion pressure (CPP) is commonly accepted to improve brain tissue oxygen pressure (PbtO2), it remains unclear whether recommended CPP targets (i. e., >60 mmHg) would result in adequate brain oxygenation in brain injured patients. The aim of this study was to identify the target of CPP associated with normal brain oxygenation.Methods: Prospectively collected data including patients suffering from acute brain injury and monitored with PbtO2, in whom daily CPP challenge using vasopressors was performed. Initial CPP target was >60 mmHg; norepinephrine infusion was modified to have an increase in CPP of at least 10 mmHg at two different steps above the baseline values. Whenever possible, the same CPP challenge was performed for the following days, for a maximum of 5 days. CPP “responders” were patients with a relative increase in PbtO2 from baseline values > 20%.Results: A total of 53 patients were included. On the first day of assessment, CPP was progressively increased from 73 (70–76) to 83 (80–86), and 92 (90–96) mmHg, which resulted into a significant PbtO2 increase [from 20 (17–23) mmHg to 22 (20–24) mmHg and 24 (22–26) mmHg, respectively; p < 0.001]. Median CPP value corresponding to PbtO2 values > 20 mmHg was 79 (74–87) mmHg, with 2 (4%) patients who never achieved such target. Similar results of CPP targets were observed the following days. A total of 25 (47%) were PbtO2 responders during the CPP challenge on day 1, in particular if low PbtO2 was observed at baseline.Conclusions: PbtO2 monitoring can be an effective way to individualize CPP values to avoid tissue hypoxia. Low PbtO2 values at baseline can identify the responders to the CPP challenge.

Effect of a temporary lying position on cerebral hemodynamic and cerebral oxygenation parameters in patients with severe brain trauma.

Temporary transition from the half-seated position (HSP) to the lying position (LyP) is often associated with an increase in intracranial pressure (ICP) during management of patients with severe traumatic brain injury (TBI). This study was designed to assess the impact of the temporary LyP on cerebral perfusion and oxygenation in cases of severe TBI. Patients with a severe blunt TBI with indication of ICP monitoring were prospectively included. Patients underwent standardized management according to the international guidelines to minimize secondary insults. For each patient, a maneuver to a LyP for 30min was performed daily during the first 7days of hospitalization. ICP, cerebral perfusion pressure (CPP), mean velocity (Vm), pulsatility index (PI), regional cerebral oxygen saturation (rScO2), jugular venous oxygen saturation (SvjO2)) were compared in the HSP and the LyP. Twenty-four 24 patients were included. The median Glasgow coma scale score was 6 (interquartile range (IQR), 3-8), the median injury severity score was 32 (IQR, 25-48), and the mean age was 39 ± 16years. On day 1, ICP (+ 6mmHg (IQR, 4-7mmHg)) and CPP (+ 10mmHg (IQR, 5-14mmHg) were significantly increased in the LyP compared with the HSP. Vm increased significantly in the LyP on the mainly injured side (+ 6cm/s (IQR, + 0-11cm/s); P = 0.01) and on the less injured side (+ 4cm/s (IQR, + 1-8cm/s); P < 0.01). rScO2 behaved similarly (+ 2 points (IQR, + 2-4 points) and + 3 points (IQR, + 2-5 points), respectively; P < 0.001). Mixed models highlighted the significant association between the position and CPP, Vm, rScO2, with more favorable conditions in the lying position. Within the first week of management, the temporary LyP in cases of severe TBI was associated with a moderate increase in CPP, Vm, and rScO2despite a moderate increase in ICP.

Comparison of equiosmolar doses of 10% hypertonic saline and 20% mannitol for controlling intracranial hypertention in patients with large hemispheric infarction

ObjectiveWe conducted this prospective self-crossover controlled trial to compare the efficacy and safety of 10 % hypertonic saline (HS) and 20 % mannitol in doses of similar osmotic burden for the treatment of increased intracranial pressure (ICP) in patients with large hemispheric infarction (LHI). Patients and MethodsPatients with LHI were enrolled from January 2017 to January 2018. We used an alternating treatment protocol to compare the effects of HS with mannitol given for episodes of increased ICP in patients with LHI. Indicators such as ICP, mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) were continuously monitored at regular intervals for 240 min after initiation of infusion. Electrolytes, plasma osmolality and renal functions were measured before and 240 min after initiation of infusion to compare the efficacy and safety of the two drugs. ResultsA total of 49 episodes of increased ICP occurred in 14 patients with LHI, of which 24 were infused with 10 % HS and 25 with 20 % mannitol. Both the treatments were equally effective in reducing ICP (P < 0.01). The differences in the duration and degree of reduction were not significant between the groups (P > 0.05). Although both the osmolar agents decreased MAP, the degree was greater in the mannitol group (P < 0.05) at T120. The increase in CPP was greater in the HS group compared with the mannitol group (P < 0.05) at T120. However, HS was associated with faster heart rate (HR) and higher serum chloride levels (P < 0.05). Changes in serum sodium levels and osmolality were not significant between the groups in spite of being higher in the HS group. ConclusionsBoth the drugs can serve as first-line agents for treating intracranial hypertension caused by LHI and should be selected rationally according to the differences in efficacy and adverse effects.

Effects of different adrenaline doses on cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs

BackgroundThe influence of adrenaline during cardiopulmonary resuscitation (CPR) on the neurological outcome of cardiac arrest survivors is unclear. As little is known about the pathophysiological effects of adrenaline on cerebral oxygen delivery and cerebral metabolism we investigated its effects on parameters of cerebral oxygenation and cerebral metabolism in a pig model of CPR. MethodsFourteen pigs were anesthetized, intubated and instrumented. After 5 min of cardiac arrest CPR was started and continued for 15 min. Animals were randomized to receive bolus injections of either 15 or 30 μg/kg adrenaline every 5 min after commencement of CPR. ResultsMeasurements included mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2), arterial and cerebral venous blood gases and cerebral microdialysis parameters, e.g. lactate/pyruvate ratio. Adrenaline induced a significant increase in MAP and CPP in all pigs. However, increases in MAP and CPP were short-lasting and tended to decrease with repetitive bolus administration. There was no statistical difference in any parameter of cerebral oxygenation or metabolism between study groups. ConclusionsBoth adrenaline doses resulted in short-lasting CPP peaks which did not translate into improved cerebral tissue oxygen tension and metabolism. Further studies are needed to determine whether other dosing regimens targeting a sustained increase in CPP, may lead to improved brain oxygenation and metabolism, thereby improving neurological outcome of cardiac arrest patients.

Brain Hypoxia Secondary to Diffusion Limitation in Hypoxic Ischemic Brain Injury Postcardiac Arrest.

We sought to characterize 1) the difference in the diffusion gradient of cellular oxygen delivery and 2) the presence of diffusion limitation physiology in hypoxic-ischemic brain injury patients with brain hypoxia, as defined by parenchymal brain tissue oxygen tension less than 20 mm Hg versus normoxia (brain tissue oxygen tension > 20 mm Hg). Post hoc subanalysis of a prospective study in hypoxic-ischemic brain injury patients dichotomized into those with brain hypoxia versus normoxia. Quaternary ICU. Fourteen adult hypoxic-ischemic brain injury patients after cardiac arrest. Patients underwent monitoring with brain oxygen tension, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and jugular venous bulb oxygen saturation. Data were recorded in real time at 300Hz into the ICM+ monitoring software (Cambridge University Enterprises, Cambridge, United Kingdom). Simultaneous arterial and jugular venous bulb blood gas samples were recorded prospectively. Both the normoxia and hypoxia groups consisted of seven patients. In the normoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen tension, and cerebral perfusion pressure were 29 mm Hg (SD, 9), 45 mm Hg (SD, 9), and 80 mm Hg (SD, 7), respectively. In the hypoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen to brain tissue oxygen tension gradient, and cerebral perfusion pressure were 14 mm Hg (SD, 4), 53 mm Hg (SD, 8), and 72 mm Hg (SD, 6), respectively. There were significant differences in the jugular venous bulb oxygen tension-brain oxygen tension gradient (16 mm Hg [sd, 6] vs 39 mm Hg SD, 11]; p < 0.001) and in the relationship of jugular venous bulb oxygen tension-brain oxygen tension gradient to cerebral perfusion pressure (p = 0.004) when comparing normoxia to hypoxia. Each 1 mm Hg increase in cerebral perfusion pressure led to a decrease in the jugular venous bulb oxygen tension-brain oxygen tension gradient by 0.36 mm Hg (95% CI, -0.54 to 0.18; p < 0.001) in the normoxia group, but no such relation was demonstrable in the hypoxia group. In hypoxic-ischemic brain injury patients with brain hypoxia, there is an elevation in the jugular venous bulb oxygen tension-brain oxygen tension gradient, which is not modulated by changes in cerebral perfusion pressure.

The Effect of Candesartan Alone and Its Combination With Estrogen on Post-traumatic Brain Injury Outcomes in Female Rats.

Aim: The aim of this study was to evaluate the effect of candesartan (angiotensin II type I receptor blocker) alone and its combination with estrogen on the changes in brain edema, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) following diffuse traumatic brain injury (TBI) in female rats.Methods: TBI was induced in ovariectomized female rats using Marmarou's method. The treatment groups received low-dose (LC) and high-dose (HC) candesartan, estrogen (E2), a combination of estrogen vehicle and candesartan vehicle (oil + vehicle), or a combination of estrogen with low-dose (E2 + LC), or with high-dose (E2 + HC) candesartan. ICP and CPP were measured before and several times after TBI, and the brain water content (brain edema) was measured 24 h after TBI.Results: After the TBI, brain edema and ICP in the estrogen group were lower than in the vehicle and TBI groups. Brain edema and ICP in the HC group were lower than in the vehicle group after TBI. Although there was no significant difference in brain edema and ICP between the LC and vehicle groups, significant differences in these variables were observed when the E2 + LC and E2 + HC groups were compared with the oil + vehicle group after TBI. A significant increase in CPP was observed in the estrogen group 4 and 24 h post-TBI, while this increase was found in the HC and E2 + LC groups 24 h post-TBI.Conclusions: A low dose of candesartan did not exert a protective effect on TBI outcomes, but such an effect did appear after combination with estrogen. This finding suggests that interaction between low-dose candesartan and estrogen improves TBI-induced consequences.

The effect of steady-state CO2 on regional brain blood flow responses to increases in blood pressure via the cold pressor test.

The pressure-passive cerebrovasculature is affected by alterations in cerebral perfusion pressure (CPP) and arterial blood gases (e.g., pressure of arterial [Pa]CO2), where acute changes in either stimulus can influence cerebral blood flow (CBF). The effect of superimposed increases in CPP at different levels of steady-state PaCO2 on regional CBF regulation is unclear. In 17 healthy participants, we simultaneously recorded continuous heart rate (electrocardiogram), blood pressure (finometer), pressure of end-tidal CO2 (PETCO2; gas analyzer), and middle (MCA) and posterior (PCA) cerebral artery blood velocity (CBV; transcranial Doppler ultrasound). Three separate CPTs were administered by passive immersion of both feet into 0-1 °C of ice water for 3-min under three randomized and coached steady-state PETCO2 conditions: normocapnia (room air), hypocapnia (-10 Torr; hyperventilation) and hypercapnia (+9 Torr; 5% inspired CO2;). CBV responses were calculated as the absolute difference (∆) between baseline and mean MCAv and PCAv during the 3-min CPT. Both the ∆MCAv and ∆PCAv responses to the CPT were larger under hypercapnic conditions. The absolute ∆MCAv response was larger than the ∆PCAv during the CPT across all three CO2 trials. Cerebrovascular CO2 reactivity (CVR) was larger in the MCA than PCA in both CPT and baseline conditions, but there were no differences in CVR between CPT and baseline conditions. Our data indicate that (a) increases in CO2 increases the CBV responses to a CPT, (b) the anterior cerebrovasculature is more responsive to a CPT-induced increases in MAP, and (c) although unchanged during a CPT, CVR is larger in the anterior cerebral circulation.

Effectiveness of 7.5% hypertonic saline in children with severe traumatic brain injury

PurposeHyperosmolar therapies aim at controlling increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI). The aim of this study was to evaluate the effect of 7.5% hypertonic saline (HTS) on ICP and cerebral perfusion pressure (CPP) in children with severe TBI. Materials and methodsMedical records of patients 14 years or younger with severe TBI, admitted in the pediatric intensive care unit of “Aghia Sophia” Children's Hospital, Athens, Greece, during 2009 to 2015, and received HTS apart from mannitol were retrospectively reviewed. The ICP and CPP pre-HTS and 30, 60, and 120 minutes post-HTS infusion were evaluated. Furthermore, the presence of adverse effects, the long-term neurological outcome, and survival were recorded. ResultsTwenty-nine patients requiring in total 136 HTS infusions were analyzed. The ICP was significantly reduced and CPP elevated at 30, 60, and 120 minutes postinfusion; and furthermore, postadministration ICP and CPP were predominantly within acceptable limits. No significant adverse effects were recorded and most of the patients survived, however, one third had severe neurological impairment at 6 months postinjury. ConclusionsIn our study, 7.5% HTS infusion as a second-tier osmotic therapy was associated with significant reduction of ICP and increase of CPP in children with severe TBI.

Monitoring of brain oxygenation during hypothermic CPR – A prospective porcine study

Background and aimLimited data are available concerning the impact of CPR interventions on cerebral oxygenation during hypothermic cardiac arrest. We therefore studied cerebral perfusion pressure (CPP), brain tissue oxygen tension (PbtO2), cerebral venous oxygen saturation (ScvO2) and regional cerebral oxygen saturation (rSO2) in an animal model of hypothermic CPR. We also assessed the correlation between rSO2 and CPP, PbtO2 and ScvO2 to clarify whether near-infrared spectroscopy (NIRS) may be used to non-invasively monitor changes in cerebral oxygenation during hypothermic CPR. MethodsNine pigs were surface-cooled to a core temperature of 28°C and underwent a period of asphyxia before cardiac arrest was induced. After 2min of untreated cardiac arrest they were resuscitated for 45min. CPP, PbtO2, ScvO2 and rSO2 were monitored after periods of stable external chest compression, a short interruption of CPR and after epinephrine administration. ResultsDuring external chest-compressions before adrenalin administration CPP, PbtO2, ScvO2 and rSO2 increased in parallel and changes in rSO2 closely correlated with changes in CPP (r=.844; p<.001) and ScvO2 (r=.868; p<.001). After adrenaline administration CPP and PbtO2 increased, ScvO2 decreased and rSO2 values did not change and there was no significant correlation between rSO2 and CPP, PbtO2, or ScvO2. ConclusionIn this animal model of hypothermic cardiac arrest adrenaline was associated with an increase in global cerebral oxygen extraction despite an increase in CPP. Discrepancies in the time course of PbtO2 and ScvO2 suggest differences in regional oxygen metabolism after adrenalin. rSO2 values correlated closely with CPP and ScvO2 only during periods of external chest compression without adrenaline administration.

Use of the intrathoracic pressure regulator to lower intracranial pressure in patients with altered intracranial elastance: a pilot study

The intrathoracic pressure regulator (ITPR) is a novel noninvasive device designed to increase circulation and blood pressure. By applying negative pressure during the expiratory phase of ventilation it decreases intrathoracic pressure and enhances venous return, which increases cardiac output. It is possible that the ITPR may both decrease intracranial pressure (ICP) and increase cerebral perfusion pressure (CPP) in brain-injured patients by decreasing cerebral venous blood volume and increasing cardiac output. The authors conducted an open-label, "first-in-humans" study of the ITPR in patients with an ICP monitor or external ventricular drain and altered intracranial elastance. This prospective randomized trial commenced July 2009. Baseline hemodynamic variables and ICP were recorded prior to inserting one of the two ITPRs into the ventilator circuit based on a randomization scheme. Depending on the device selected, activation provided either -5 or -9 mm Hg endotracheal tube pressure. Hemodynamic and ICP data were recorded sequentially every 2 minutes for 10 minutes. The first device was turned off for 10 minutes, then it was removed and the second device was applied, and then the procedure was repeated for the second device. Ten patients with elevated ICP secondary to intracranial hemorrhage (n = 4), trauma (n = 2), obstructive hydrocephalus (n = 2), or diffuse cerebral processes (n = 2) were enrolled. Baseline ICP ranged from 12 to 38 mm Hg. With device application, a decrease in ICP was observed in 16 of 20 applications. During treatment with the -5 mm Hg device, there was a mean maximal decrease of 3.3 mm Hg in ICP (21.7 vs 18.4 mm Hg, p = 0.003), which was associated with an increase in CPP of 6.5 mm Hg (58.2 vs 64.7 mm Hg, p = 0.019). During treatment with the -9 mm Hg device, there was a mean maximal decrease of 2.4 mm Hg in ICP (21.1 vs 18.7 mm Hg, p = 0.044), which was associated with an increase in CPP of 6.5 mm Hg (59.2 vs 65.7 mm Hg, p = 0.001). This pilot study demonstrates that use of the ITPR in patients with altered intracranial elastance is feasible. Although this study was not powered to demonstrate efficacy, these data strongly suggest that the ITPR may be used to rapidly lower ICP and increase CPP without apparent adverse effects. Additional studies will be needed to assess longitudinal changes in ICP when the device is in use and to delineate treatment parameters.

Effect of Cerebral Perfusion Pressure on Cerebral Cortical Microvascular Shunting at High Intracranial Pressure in Rats

Recently, we showed that decreasing cerebral perfusion pressure (CPP) from 70 mm Hg to 50 mm Hg and 30 mm Hg by increasing intracranial pressure (ICP) with a fluid reservoir induces a transition from capillary (CAP) to microvascular shunt (MVS) flow in the uninjured rat brain. This transition was associated with tissue hypoxia, increased blood-brain barrier (BBB) permeability, and brain edema. Our aim was to determine whether an increase in CPP would attenuate the transition to MVS flow at high ICP. Rats were subjected to progressive, step-wise increases in ICP of up to 60 mm Hg by an artificial cerebrospinal fluid reservoir connected to the cisterna magna. CPP was maintained at 50, 60, 70, or 80 mm Hg by intravenous dopamine infusion. Microvascular red blood cell flow velocity, BBB integrity (fluorescein dye extravasation), and tissue oxygenation (nicotinamide adenine dinucleotide) were measured by in vivo 2-photon laser scanning microscopy. Doppler cortical flux, rectal and cranial temperatures, ICP, arterial blood pressure, and gases were monitored. The CAP/MVS ratio increased (P<0.05) at higher ICP as CPP was increased from 50 to 80 mm Hg. At an ICP of 30 mm Hg and CPP of 50 mm Hg, the CAP/MVS ratio was 0.6±0.1. At CPP of 60, 70, and 80 mm Hg, the ratio increased to 0.9±0.1, 1.4±0.1, and 1.9±0.1, respectively (mean±SEM; P<0.05). BBB opening and increase of reduced form of nicotinamide adenine dinucleotide occurred at higher ICP as CPP was increased. Increasing CPP at high ICP attenuates the transition from CAP to MVS flow, development of tissue hypoxia, and increased BBB permeability.

Decompressive craniectomy: a meta-analysis of influences on intracranial pressure and cerebral perfusion pressure in the treatment of traumatic brain injury

In recent years, the role of decompressive craniectomy for the treatment of traumatic brain injury (TBI) in patients with refractory intracranial hypertension has been the subject of several studies. The purpose of this review was to evaluate the contribution of decompressive craniectomy in reducing intracranial pressure (ICP) and increasing cerebral perfusion pressure (CPP) in these patients. Comprehensive literature searches were performed for articles related to the effects of decompressive craniectomy on ICP and CPP in patients with TBI. Inclusion criteria were as follows: 1) published manuscripts, 2) original articles of any study design except case reports, 3) patients with refractory elevated ICP due to traumatic brain swelling, 4) decompressive craniectomy as a type of intervention, and 5) availability of pre- and postoperative ICP and/or CPP data. Primary outcomes were ICP decrease and/or CPP increase for assessing the efficacy of decompressive craniectomy. The secondary outcome was the persistence of reduced ICP 24 and 48 hours after the operation. Postoperative ICP values were significantly lower than preoperative values immediately after decompressive craniectomy (weighted mean difference [WMD] -17.59 mm Hg, 95% CI -23.45 to -11.73, p < 0.00001), 24 hours after (WMD -14.27 mm Hg, 95% CI -24.13 to -4.41, p < 0.00001), and 48 hours after (WMD -12.69 mm Hg, 95% CI -22.99 to -2.39, p < 0.0001). Postoperative CPP was significantly higher than preoperative values (WMD 7.37 mm Hg, 95% CI 2.32 to 12.42, p < 0.0001). Decompressive craniectomy can effectively decrease ICP and increase CPP in patients with TBI and refractory elevated ICP. Further studies are necessary to define the group of patients that can benefit most from this procedure.

Improved cerebral perfusion pressures and 24-hr neurological survival in a porcine model of cardiac arrest with active compression-decompression cardiopulmonary resuscitation and augmentation of negative intrathoracic pressure*

Generation of negative intrathoracic pressure during the decompression phase of cardiopulmonary resuscitation enhances the refilling of the heart. We tested the hypothesis that when compared with closed-chest manual compressions at 80 chest compressions per min, treatment with active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min combined with augmentation of negative intrathoracic pressure would lower intracranial pressure and increase cerebral perfusion, thereby improving neurologically intact survival rates following prolonged untreated cardiac arrest. Prospective, randomized animal study. Animal laboratory facilities. A total of 26 female farm pigs in two different protocols (n = 17 and n = 9). Seventeen pigs were subjected to 8.5 mins of untreated ventricular fibrillation and prospectively randomized to cardiopulmonary resuscitation at 80 chest compressions/min or active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min plus an impedance threshold device. Coronary perfusion pressures (29.5 ± 2.7 mm Hg vs. 22.4 ± 1.6 mm Hg, p = .03), carotid blood flow (44.0 ± 12.2 vs. 30.9 ± 10.4, p = .03), and 24-hr neurological survival (88% vs. 22%, p = .015) were higher with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device. Cerebral perfusion pressures, measured in nine additional pigs, were improved with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device (21.9 ± 1.2 mm Hg vs. 8.9 ± 0.8 mm Hg, p < .0001). With active compression-decompression cardiopulmonary resuscitation + impedance threshold device, mean diastolic intracranial pressure during decompression was lower (12.2 ± 0.2 mm Hg vs. 16.6 ± 1.2 mm Hg, p = .02) and the downward slope of the decompression phase intracranial pressure curve was steeper (-60.3 ± 12.9 mm Hg vs. -46.7 ± 11.1 mm Hg/sec, p < .001). Active compression-decompression cardiopulmonary resuscitation + an impedance threshold device increased cerebral perfusion pressures and lowered diastolic intracranial pressure and intracranial pressure rate during the decompression phase. These mechanisms may underlie the observed increase in cerebral perfusion pressure, carotid blood flow, and survival rates with favorable neurologic outcomes in this pig model of cardiac arrest.

Chapter 15. Analgesics, sedatives, and neuromuscular blockade

Chapter 15. Analgesics, sedatives, and neuromuscular blockade

Chapter 8. Hyperosmolar therapy

Chapter 8. Hyperosmolar therapy

To wake-up, or not to wake-up: that is the Hamletic neurocritical care question!

The need for a reliable neurological evaluation in severely brain-injured patients conflicts with sedation, which is routinely administered. Helbok and colleagues prospectively evaluated in a small cohort of 20 sedated severely brain-injured patients the effects of a wakeup test on intracranial pressure (ICP), brain tissue oxygen tension and brain metabolism. The test has been considered potentially risky on 34% of the study days. When the test is performed, ICP and cerebral perfusion pressure increase, usually slightly, except in a subgroup of patients with lower cerebral compliance where marked ICP and cerebral perfusion pressure changes were recorded. In this cohort, the information gained with the wake-up test has been negligible. Given the current little knowledge about the benefits of interruption of continuous sedation in brain-injured patients, it is extremely important to adopt multiple monitoring modalities in neurocritical care in order to escape wake-up tests in those patients who will potentially be harmed by this procedure. Once the clinical condition will improve, sedation needs to be tapered and suspended as soon as possible.

Intracranial variables in propofol or sevoflurane-anesthestized dogs subjected to subarachnoid administration of iohexol

The effects of subarachnoid administration of iohexol on intracranial hemodynamic in dogs anesthetized with propofol or sevoflurane were evaluated. Thirty adult animals (10.9±2.9kg) were distributed into two groups: PG, where propofol was used for induction (10±0.5mg/kg), followed by a continuous rate infusion at 0.55±0.15mg/kg/hour, and SG, where sevoflurane was administered for induction (2.5 MAC) and for anesthetic maintenance (1.5 MAC). A fiberoptic catheter was implanted on the right superficial cerebral cortex to monitor intracranial pressure (ICP). After 30 minutes, cerebrospinal fluid (CSF) was collected at the cisterna magna and iohexol was injected. The measurements were performed before CSF collection (TA), after the iohexol injection (T0), and at 10-minute intervals (T10 to T60). Intracranial pressure decreased at T0 in SG. Cerebral perfusion pressure at T0 was higher than at TA, T50 and T60 in PG, but in SG, the mean value at T0 was higher than the ones from T20 to T60. Mean arterial pressure at T0 was higher than at TA in PG, while in SG, the values from T20 to T60 were lower than at T0. The heart rate at T60 was lower than at T0 in PG. Cardiac output at TA was lower than at T60 in SG. The cerebrospinal fluid collection and administration of iohexol promoted decrease in intracranial pressure in sevolflurane-anesthetized dogs and increase in cerebral perfusion pressure in propofol-anesthetized dogs.