Studies on supratentorial subdural bleeding using a porcine model.

To the Editor. —Dr Lavin states: Certainly, if the blood pressure is to be reduced in patients with cerebral hemorrhage, it should be done cautiously, not aggressively with a short-acting hypotensive agent such as sodium nitroprusside....1 Many would argue that sodium nitroprusside is not the agent of choice since intracranial pressure has been observed to increase dramatically in some cases with a decrease in cerebral perfusion pressure.2In fact, in the first case report Dr Lavin presented, hydralazine's effect could have been mediated through a rise in intracranial pressure rather than a decrease in systemic arterial pressure. Only by simultaneously measuring intracranial and systemic arterial pressures can we accurately know cerebral perfusion pressure, and only then can we guess at regional blood flow. For it is regional blood flow that is really our concern when speaking of ischemic nervous tissue. Many intensivists prefer trimethaphan camsylate for its minimal

Fiberoptic bronchoscopy (FB) plays an important role in making the diagnosis of nosocomial pneumonia and resolving lobar atelectasis in critically injured trauma patients. It has been shown to be a safe procedure with only occasional complications. However, in patients with head injuries, FB can lead to intracranial hypertension. Sustained increases in intracranial pressure (ICP) leads to poor outcome in these patients. Because of this, a prospective study was done not only to assess the effect of FB on ICP and cerebral perfusion pressure (CPP) in patients with brain injuries, but also to identify a regimen of sedation and anesthesia that could prevent significant increases in ICP during FB. Twenty-six FB were performed in 23 patients with ICP monitors or ICP monitors and ventriculostomy drains in place for Glasgow Coma Scale score < 8 or management of postcraniotomy trauma. FB was performed to aid in the diagnosis of nosocomial pneumonia or to aid in resolving lobar atelectasis. Before FB, all patients received a standard anesthetic regimen consisting of vecuronium (10 mg), morphine sulfate (4 mg), and midazolam (2.5 mg). Patients with diminished cranial compliance, defined as ICP > 10 mm Hg, also received a nebulizer treatment of 3 mL of 4% lidocaine before FB. All patients were preoxygenated with FIO2 = 1.0 for 10 minutes. Intracranial pressure, mean arterial pressure, and CPP were monitored continuously throughout the procedure. These same variables were also recorded at baseline and at 2-minute intervals during the procedure. The time to return to baseline ICP was also recorded. The mean ICP at baseline (immediately before FB) was 12.6 mm Hg. After introduction of the bronchoscope, the ICP rapidly increased in 21 procedures (81%) and the mean highest ICP was 38.0 mm Hg. There was also a concomitant increase in mean arterial pressure such that there was no substantial change in CPP. The mean lowest CPP was 73.1 mm Hg. The average time for return of ICP to baseline was 13.9 minutes. In the subgroup of patients with ICP > 10, attempting to blunt the tracheal stimulation by anesthetizing the trachea with 4% nebulized lidocaine did not seem to be successful. The mean highest ICP in this subgroup was 41.8 mm Hg. The CPP changed in a similar manner, as the mean lowest CPP was 74.0 mm Hg. The mean time to return to baseline was 12.5 minutes. No patient had acute neurologic deterioration secondary to FB. Although FB is an important procedure in the pulmonary care of head injured patients, it produces substantial, but transient, increases in ICP and should be used with caution in patients with diminished cranial compliance. Sedation, analgesia, paralysis, and topical tracheal anesthesia did not completely prevent the rise in ICP. Although no acute deterioration in condition occurred, secondary brain injury caused by localized cerebral ischemia is certainly possible. Because of the substantial increases in ICP, herniation may be precipitated in an occasional patient. Further study is needed to identify a regimen that will confer protection.

Patient position change and tracheal suctioning are routine interventions in mechanically ventilated traumatic brain injury (TBI) patients. We sought to better understand the impact of these interventions on intracranial pressure (ICP) and cerebral hemodynamics. We conducted a prospective study in TBI patients requiring ICP monitoring. The timing of position changes and suctioning episodes were recorded with concurrent blood pressure and ICP measurements. We collected data on 460 patient position changes and 204 suctioning episodes over 2404 h in 18 ventilated patients (mean age 34 [13] years, median Glasgow Coma Score 4 [3-7]). We recorded 24 (20-31) positioning and 11 (6-18) suctioning episodes per patient, with 54% and 39% of position changes associated with ICP ≥22 mm Hg and cerebral perfusion pressure (CPP) <60 mm Hg, respectively, and 22% and 27% of suctioning episodes associated with an ICP ≥22 mm Hg and CPP <60 mm Hg. The median change in ICP was 11 (6-16) mm Hg after position changes and 3 (1-9) mm Hg after suctioning. Reduction in CPP to <60 mm Hg lasted ≥10 min in 17% of positioning and 11% of suctioning episodes. The baseline ICP and its amplitude were both predictive of a rise in ICP ≥22 mm Hg after positioning and suctioning episodes, whereas cerebral autoregulation was not. Baseline CPP was predictive of a decrease in CPP <60 mm Hg after both interventions. Increases in ICP and reductions in CPP are common following patient positioning and tracheal suctioning episodes. Frequently, these changes are substantial and sustained.

Targets for treatment of raised intracranial pressure or decreased cerebral perfusion pressure in pediatric neurocritical care are not well defined. Current pediatric guidelines, based on traumatic brain injury, suggest an intracranial pressure target of less than 20 mm Hg and cerebral perfusion pressure minimum of 40-50 mm Hg, with possible age dependence of cerebral perfusion pressure. We sought to define intracranial pressure and cerebral perfusion pressure thresholds associated with inhospital mortality across a large single-center pediatric neurocritical care cohort. Retrospective chart review. PICU, single quaternary-care center. Individuals receiving intracranial pressure monitoring from January 2012 to December 2016. None. Intracranial pressure and cerebral perfusion pressure measurements from 262 neurocritical care patients (87 traumatic brain injury and 175 nontraumatic brain injury; 63% male; 8.3 ± 5.8 yr; mortality 11.1%). Mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.75 and 0.64, respectively, for association of inhospital mortality. Cerebral perfusion pressure cut points increased with age (< 2 yr = 47, 2 to < 8 yr = 58 mm Hg, ≥ 8 yr = 73 mm Hg). In the traumatic brain injury subset, mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.70 and 0.78, respectively, for association of inhospital mortality. Traumatic brain injury cerebral perfusion pressure cut points increased with age (< 2 yr = 45, 2 to < 8 yr = 57, ≥ 8 yr = 68 mm Hg). Mean intracranial pressure greater than 15 mm Hg, male sex, and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 14.23 [5.55-36.46], 2.77 [1.04-7.39], and 2.57 [1.03-6.38], respectively; all p < 0.05). Mean cerebral perfusion pressure less than 67 mm Hg and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 5.16 [2.05-12.98] and 3.71 [1.55-8.91], respectively; both p < 0.01). In the nontraumatic brain injury subset, mean intracranial pressure had an area under the receiver operating characteristic curve 0.77 with an intracranial pressure cut point of 15 mm Hg, whereas mean cerebral perfusion pressure was not predictive of inhospital mortality. We identified mean intracranial pressure thresholds, utilizing receiver operating characteristic and regression analyses, associated with inhospital mortality that is below current guidelines-based treatment targets in both traumatic brain injury and nontraumatic brain injury patients, and age-dependent cerebral perfusion pressure thresholds associated with inhospital mortality that were above current guidelines-based targets in traumatic brain injury patients. Further study is warranted to identify data-driven intracranial pressure and cerebral perfusion pressure targets in children undergoing intracranial pressure monitoring, whether for traumatic brain injury or other indications.

Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow.

To test the hypothesis that isoflurane-anesthetized horses during controlled ventilation and spontaneous ventilation exhibit temporal changes in cerebral hemodynamics, as measured by intracranial pressure and cerebral perfusion pressure, that reflect temporal changes in systemic arterial pressure. 6 healthy adult horses. Horses were anesthetized in left lateral recumbency with 1.57% isoflurane in O2 for 5 hours in 2 experiments by use of either controlled ventilation (with normocapnia) or spontaneous ventilation (with hypercapnia) in a randomized crossover design. Intracranial pressure was measured with a subarachnoid strain-gauge transducer. Carotid artery pressure, central venous pressure, airway pressures, blood gases, and minute ventilation also were measured. Intracranial pressure during controlled ventilation significantly increased during constant dose isoflurane anesthesia and thus contributed to decreasing cerebral perfusion pressure. Intracranial pressure was initially higher during spontaneous ventilation than during controlled ventilation, but this difference disappeared over time; no significant differences in cerebral perfusion pressures were observed between horses that had spontaneous or controlled ventilation. Cerebral hemodynamics and their association with ventilation mode are altered over time in isoflurane-anesthetized horses and could contribute to decreased cerebral perfusion during prolonged anesthesia.

The primary mechanism of intracranial pressure (ICP) adaptation to acute increases in arterial pressure (AP) is through autoregulation to maintain cerebral perfusion pressure (CPP). However, this mechanism is impaired in hypertension. We previously demonstrated that male rats with renovascular hypertension, which presents high renin-angiotensin system (RAS) activity, showed increased baseline levels of ICP and CPP compared to normotensive rats. Therefore, in the present study we aimed to evaluate the baseline levels of ICP and CPP in Dahl Salt-Sensitive (DSS) rats, a hypertensive model independent of high RAS activity and to assess the effects of increasing intracranial volume with intracerebroventricular (ICV) infusion of saline (0.15 M NaCl) on ICP and CPP. Male and female DSS rats (3-4 months of age) were used and randomly assigned to be fed with a normal salt diet (DSS-NS; 0.6% NaCl) or high salt diet (DSS-HS; 4% NaCl) for three weeks. After this period, rats were anaesthetized with (urethane,1.4 g/Kg, i.p.), tracheostomized, and one catheter was inserted in the femoral artery for mean AP (MAP) recording and other catheter was inserted in the right lateral ventricle (LV) for ICP recording. A needle was placed in the left LV to infuse 100 µl of saline for 10 min (10 µL/min rate). CPP was calculated by subtracting MAP and ICP. Male and female DSS-HS rats presented higher baseline MAP compared to their NS pairs (Male: 124 ± 9, vs NS: 90 ± 10 and Female: 134 ± 11, vs NS: 100 ± 8 mmHg, respectively; p &lt; 0.05). While MAP was not changed during ICV infusion in males DSS-HS and NS, it was decreased in female DSS-HS compared to the baseline and DSS-NS (-13 ± 5 mmHg at 10 min of infusion, p &lt; 0.05). Baseline ICP was comparable in male DSS-HS and NS (7.1 ± 2.3, vs NS: 8.1 ± 0.6 mmHg; p &gt; 0.05), as well as the increase in ICP during the ICV infusion. Conversely, in the females, baseline ICP was greater in DSS-HS compared to NS (5.6 ± 2, vs NS: 1.7 ± 1.9 mmHg; p &lt; 0.05), but ICP increased similarly in HS and NS during the ICV infusion. Baseline CPP was higher in male and female DSS-HS compared to their NS pairs (Male: 117 ± 5, vs NS: 82 ± 4 and Female: 128 ± 4, vs NS: 98 ± 5 mmHg, respectively; p &lt; 0.05). During the ICV infusion, there was a decrease in CPP in male DSS-HS (-8.0 ± 4 at 10 min of infusion; p &lt; 0.05) and in the female DSS-HS (-22 ± 5 mmHg at 10 min of infusion; p &lt; 0.05) compared to their baseline and to the NS pairs. DSS-NS male and female did not present any change in CPP during ICV infusion. Although there are sex-specific differences in baseline ICP and in MAP responses to increased ICV infusion, an HS diet affects the ability to control CPP in both male and female DSS rats adequately. CNPq and CAPES Print (88887.194785/2018-00) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

1. This study investigated the effects of blocking the AT1 angiotensin receptors with irbesartan, either peripherally or centrally, on systemic blood pressure, intracranial pressure and cerebral perfusion pressure following experimental subarachnoid haemorrhage (SAH) in urethane-anaesthetized rats. Sympathetic nervous activation was determined by measuring plasma noradrenaline levels. 2. In untreated animals, SAH induced a sustained increased in intracranial pressure from 2.1 +/- 0.3 to 16 +/- 2 mmHg (3 h, P < 0.001). Cerebral perfusion pressure was reduced by 20 % (P < 0.001), this reduction being maintained for 3 h. Sympathetic activation was evident in the high level of plasma noradrenaline measured 3 h post-SAH (751 +/- 104 vs. 405 +/- 33 pg ml(-1), P < 0.05). 3. Acute peripheral pretreatment with irbesartan (3 mg kg(-1), I.V.) prevented the rise in plasma noradrenaline and further aggravated the decrease in cerebral perfusion pressure by producing transient systemic hypotension (blood pressure was 85 +/- 6 mmHg at 2 h post-SAH vs. 100 +/- 3 mmHg, P < 0.01). 4. Intracisternal pretreatment with irbesartan (0.035 mg) did not prevent the rise in plasma noradrenaline post-SAH but enhanced the rise in intracranial pressure by 75 % compared with untreated animals. 5. This study demonstrates that peripheral endogenous angiotensin II interacts with the sympathetic nervous system in order to maintain an adequate cerebral perfusion following SAH. Endogenous angiotensin II in the brain seems to exert a protective effect by counteracting the elevation in intracranial pressure that occurs following experimental SAH.

To the Editor: Sir, the study by Canhao and colleagues made the important point that the most frequent cause of death in patients with cerebral venous thrombosis (CVT) is transtentorial herniation and that these patients may potentially have benefited from decompressive hemicraniectomy.1 We would like to corroborate this argument by providing evidence for a rise in intracranial pressure (ICP) preceding brain herniation and death in a patient with CVT. A 29-year-old pregnant woman who presented with confusion and vomiting was admitted to a district general hospital. A right-sided weakness developed within 2 days. A CT brain scan showed a left temporal hemorrhage without mass effect. Her Glasgow Coma Scale score dropped to 8/15; she was intubated and transferred to the neurocritical care …

The effect of gammahydroxybutyrate (GHB) on ICP, systemic arterial pressure and cerebral perfusion pressure in the experimentally induced brain oedema of the rat was examined. 400 mg/kg GHB reduced significantly ICP (11.74 +/- 1.20 mm Hg; control: 16.20 +/- 8.89 mm Hg; p less than 0.01) while increasing mean systemic arterial pressure (109.89 +/- 6.35 mm Hg; control: 89.65 +/- 4.22 mm Hg; p less than 0.05) and cerebral perfusion pressure (98.11 +/- 6.79 mm Hg; control: 73.84 +/- 5.25 mm Hg; p less than 0.02). In the dose-effect curve 200 mg/kg GHB show an increase in mean systemic arterial pressure from 89.60 +/- 9.35 mm Hg to 97.60 +/- 3.48 mm Hg (p less than 0.02) and 400 mg/kg GHB to 108.00 +/- 5.20 mm Hg (p less than 0.001) mean systemic arterial pressure. Thus, the decrease in intracranial pressure is not due to a reduction in the mean systemic arterial pressure, but GHB does reduce the ICP while increasing mean systemic arterial pressure and cerebral perfusion pressure. GHB may be a useful adjunct to neurosurgical therapy in controlling elevated ICP.

The present experiments provide the first description of the afferent discharge characteristics of renal mechanosensitive receptors in the nonhuman primate. Twenty-seven single units with mechano-sensitive receptor activity were obtained. Afferent discharge occurred regularly (pulse synchronous) or irregularly (pulse asynchronous) under spontaneous respiration. The activity of pulse synchronous units was increased by partial occlusion of the renal vein and elevation of arterial pressure. Impulse activity decreased or disappeared during bleeding or renal arterial occlusion. The impulse activity of pulse asynchronous units was increased by partial occlusion of the renal vein. The impulse activity of silent units was induced only by partial occlusion of the renal vein. An increase in ureteral pressure (50 mmHg) produced an increase or induced impulse activity in only three of the 27 fibers tested. Compression of the kidney or renal venous occlusion was associated with a decrease in systemic arterial pressure, whereas renal arterial occlusion produced a rise in systemic arterial pressure. An increase in ureteral pressure (50 mmHg) did not produce a change in arterial pressure.

Acute hypotension produced by the intravenous injection of 20 μg/kg of rattlesnake (Crotalus atrox) venom in sheep was spontaneously restored within frac12—2 hr (crotalin collapse). Slow continuous intravenous infusion of larger doses of crotalin produced a fall in cardiac output and systemic arterial pressure, hemoconcentration, and hypoventilation. This condition could only be reversed by therapeutic intervention and was termed “crotalin shock.” Administration of antivenin in crotalin shock proved to be ineffective. Intravenous dextran infusion restored cardiac output and accentuated respiratory depression. Administration of steroids in conventional therapeutic doses resulted in a rise in systemic arterial pressure and alveolar ventilation with little change in blood flow. Simultaneous administration of dextran and corticosteroids gave better results than either material used alone. Continuous intravenous infusion of isoproterenol improved alveolar ventilation and restored spontaneous breathing in some cases of crotalin-induced respiratory arrest. dextran; ventilation; steroids; antivenin; isoproterenol; respiratory failure; hemoconcentration Submitted on September 29, 1964

In order to evaluate the safe ligation time and sites of dural venous sinuses during neurosurgical operation, systemic arterial pressure(SAP), cerebral perfusion perssure(CPP), intracranial pressure (ICP) and intrasinal pressure(ISP) were measured in cats through neuromonitor before and after obstruction of anterior 1/3, middle 1/3, posterior 1/3 of the superior sagittal sinus and the results were as follows. There were no significant increases of pressures after obstruction of anterior 1/3 of the superior sagittal sinus. In the obstructed middle 1/3 of the superior sagittal sinus group, significant increases were seen un the m-SAP within 2, 4 and 6 minutes, the m-ICP within 2-7 minutes, the m-ISP within 1-4 minutes after obstruction. In the obstructed posterior 1/3 of the superior sagittal sinus group, there were significant increases of m-SAP within 2, 4 and 6 minutes, the m-ICP within 2-7 minutes, the m-ISP within 1-3 minutes. In the obstructed Torcular Herophili group, there were significant increases of the m-SAP within 1-2 and 4-7 minutes, the m-ICP within 3-6 minutes and the m-ISP within 1-7 minutes and less significant dercreases of the m-CPP within 5-7 minutes after obstruction. In the obstructed right transverse sinus group, significant increases of the m-ICP and the m-ISP were seen within 1-7 minutes after obstruction, there were no remarkable changes in the obstructed left transverse sinus group.

The mean cerebral blood flow (CBF) has generally been demonstrated to be lower in normal pressure hydrocephalus (NPH) than in normal controls. We investigated the distribution of the regional peri- and paraventricular white matter CBF (WM CBF) in NPH at baseline and during a controlled rise in intracranial pressure (ICP). Twelve patients with idiopathic NPH (mean age 69 years) underwent a CSF infusion study. CBF was measured by H2(15)O PET at baseline and then during the steady-state plateau of raised ICP. The PET images were co-registered and resliced to 3D structural T1-weighted MRIs. Ten healthy normal volunteers served as control subjects for baseline CBF determination only. Profiles of the regional distribution of the baseline WM CBF and of the percentage change in WM CBF as a function of distance from the ventricles were plotted. The global mean baseline CBF in patients (28.4 +/- 5.2 ml/100 ml/min) was lower than in the control subjects (33 +/- 5.4 ml/100 ml/min) (P < 0.005). In patients, the profile of the regional WM CBF at baseline showed an increase with distance from the ventricles (P < 0.0001), with a maximal reduction adjacent to the ventricles and progressive normalization with distance, whereas in controls no relationship was apparent (P = 0.0748). In 10 patients, the rise in ICP during the infusion produced a fall in cerebral perfusion pressure (CPP) and a significant decrease of the global mean CBF from 27.6 +/- 3.1 to 24.5 +/- 2.9 ml/100 ml/min (P < 0.0001). The profile of the percentage changes in regional WM CBF in patients showed a U-shaped relationship with distance from the ventricles (P = 0.0007), with a maximal decrease skewed on the side of the lateral ventricles at around a mean distance of 9 mm. The WM CBF is reduced in NPH, with an abnormal gradient from the lateral ventricles towards the subcortical WM. An excessive decrease in CBF is brought about by reductions in CPP and appears to be maximal in the paraventricular watershed region. These results are discussed in the light of previous hypotheses concerning the aetiology of periventricular CBF reduction in NPH.

The effect of indomethacin, a cyclooxygenase inhibitor, was studied in the treatment of 10 patients with head injury and one patient with spontaneous subarachnoid hemorrhage, each of whom presented with high intracranial pressure (ICP) (34.4 +/- 13.1 mm Hg) and cerebral perfusion pressure (CPP) impairment (67.0 +/- 15.4 mm Hg), which did not improve with standard therapy using mannitol, hyperventilation, and barbiturates. The patient had Glasgow Coma Scale scores of 8 or less. Recordings were made of the patients' ICP and mean arterial blood pressure from the nurse's end-hour recording at the bedside, as well as of their CPP, rectal temperature, and standard therapy regimens. The authors assessed the effects of an indomethacin bolus (50 mg in 20 minutes) on ICP and CPP; an indomethacin infusion (21.5 +/- 11 mg/hour over 30 +/- 9 hours) on ICP, CPP, rectal temperature, and standard therapy regimens (matching the values before and during infusion in a similar time interval); and discontinuation of indomethacin treatment on ICP, CPP, and rectal temperature. The indomethacin bolus was very effective in lowering ICP (p < 0.0005) and improving CPP (p < 0.006). The indomethacin infusion decreased ICP (p < 0.02), but did not improve CPP and rectal temperature. The effects of standard therapy regimens before and during indomethacin infusion showed no significant changes, except in three patients in whom mannitol reestablished its action on ICP and CPP. Sudden discontinuation of indomethacin treatment was followed by significant ICP rebound. The authors suggest that indomethacin may be considered one of the frontline agents for raised ICP and CPP impairment.