Brain natriuretic peptide and fluid volume homeostasis—studies during cardiopulmonary bypass surgery

Brain natriuretic peptide (BNP) is a recently identified cardiac ventricular hormone with diuretic, natriuretic and vasorelaxant properties. The aim of our study was to examine whether serial changes in endogenous levels of BNP were associated with fluid volume homeostasis following cardiopulmonary bypass.We studied nine patients undergoing elective cardiac surgery for the repair of cardiac abnormalities requiring cardiopulmonary bypass. Urinary levels of cyclic guanosine monophosphate (cGMP), sodium, urine output, fluid balance, and plasma levels of BNP, aldosterone, plasma renin activity (PRA) and central venous pressure (CVP) were measured before, during and after cardiopulmonary bypass.Basal pre-operative plasma BNP levels were highly elevated in all nine patients with cardiac abnormalities. During bypass, pre-operative levels of BNP, urinary cGMP and plasma aldosterone decreased significantly (p < 0.05), whereas pre-operative levels of urinary sodium and PRA were slightly reduced. During recovery following bypass levels of urinary cGMP, sodium, PRA and aldosterone returned to basal pre-operative values, whereas post-operative levels of plasma BNP were found to be three-fold below basal pre-operative levels. CVP (4.3 ± 0.2 mmHg) during the onset of bypass increased significantly (p < 0.05) at the end of bypass (9 ± 0.3 mmHg) followed by a modest increase post-operatively (10 ± 0.4 mmHg). After operation only BNP had a significant correlation with urine output (r= –0.82,p < 0.02) and net fluid balance (r = –0.84,p < 0.01), whereas urinary cGMP, PRA and aldosterone all exhibited a non-significant correlation with urine output. The overall plasma BNP levels showed a non-significant positive correlation with urinary cGMP (r = 0.58,p = 0.12), CVP (r = 0.53,p = 0.3), aldosterone (r = 0.53,p = 0.2) and PRA (r = 0.63,p = 0.075). The strong association between changes in endogenous BNP with urine output and fluid balance provides evidence for involvement of BNP in the regulation of fluid volume homeostasis.     

Subdural intracranial pressure monitoring in craniosynostosis: its role in surgical management

In the management of craniosynostosis subdural intracranial pressure (ICP) monitoring has proved a useful and safe means of identifying those children with raised ICP who are at risk from its long-term sequelae and who would benefit from early surgical intervention. Overnight subdural ICP recordings have been obtained in 136 unoperated cases of craniosynostosis. Fifteen patients were studied both before and after cranial vault remodelling procedures. ICP was raised (>15 mmHg) in 35%, borderline (10–15 mmHg) in 27% and normal (<10 mmHg) in 27% of cases. Raised ICP was present in 28/53 of the syndromic craniofacial dysostosis cases and in 20/83 non-syndromic craniosynostosis cases investigated (P<0.001). Raised mean ICP and periodic plateaux of sustained ICP during sleep were particularly associated with the syndromic cases. Of the 15 patients studied following cranial vault surgery, 9 showed a reduction in ICP, 3 were unchanged and 3 had higher ICP postoperatively. The results of ICP monitoring can contribute significantly to formulating a rational and staged surgical management plan incorporating the need to normalise ICP and correct the frequently severe functional and cosmetic consequences of these disorders.     

Pressure compensation in shunt-dependent hydrocephalus with CSF shunt malfunction

This study is a retrospective analysis of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) data from 56 children with active hydrocephalus and cerebrospinal fluid (CSF) shunt malfunction. The pressures were measured from a separately sited CSF access device placed in the frontal horn of the lateral ventricle. Of the patients, 79% had an elevated ICP (mean 20±12 mmHg). A subgroup of patients demonstrated ten different forms of CSF-filled swelling. This group had significantly lower ICP recordings (P=0.000075) with a mean ICP of 8.5 mmHg compared with the remainder (22.9 mmHg). This pressure ’compensation’ was because of additional nonphysiological accommodation of CSF volume. Overall the CPP was normal in 35% of cases despite normal ICP occurring in only 11% of cases. The CPPs were not significantly different in those with and without compensation. Measurement of ICP may not always be a reliable indicator of shunt malfunction in shunt- dependent children who present with compensatory CSF-filled spaces. Received: 10 March 2000     

Naturalistic activation of barosensitive afferents release substance P in the nucleus tractus solitarius of the cat

The role for substance P (SP) in baroreceptor transmission in the nucleus tractus solitarius (NTS) remains an area of active research. The purpose of the present study was to determine whether naturalistic activation of barosensitive afferent fibers in the glossopharygneal and vagus nerves release SP in the caudal NTS. Experiments were performed on chloralose anesthetized, artificially ventilated and paralyzed cats. A microdialysis probe was stereotaxically positioned unilaterally in the NTS. Dialysate samples were collected and SP-like immunoreactivity (SP-LI) was measured by radioimmunoassay. Barosensitive afferents were mechanically activated by inflation of a balloon catheter positioned in the thoracic aorta at heart level. Graded balloon inflation produced increases in mean arterial pressure (MAP) of 33±5 mmHg and 60±3 mmHg (P<0.05) and evoked proportional baroreflex decreases in heart rate of 8±3 b.p.m. and 19±3 b.p.m. (P<0.05). This was accompanied by increases in SP-LI of 16±3% and 39±8%, respectively (P<0.05). A positive linear relationship was found between changes in MAP and SP-LI (slope=1.73 fmol/μl/mmHg, r²=0.62) that was completely abolished following barodenervation. These findings provide evidence that naturalistic activation of pressure-sensitive afferents in the glossopharygneal and vagus nerves release SP in a region of the NTS that receives primary afferent projections from aortic, carotid sinus and cardiac receptors in the cat.     

Urinary phenylethylamine correlates positively with hypomania,and negatively with depression,paranoia, and social introversion on the MMPI

Summary It has been suggested that phenylethylamine (PEA) may play a role in the modulation of affective behavior. The aim of the present study was to test this hypothesis. Urinary PEA excretion was determined in 32 drug-free healthy volunteers, and the MMPI was used for personality assessment. In support of this hypothesis, a significant positive correlation between PEA and hypomania (r = 0.50; P < 0.05) and a significant negative correlation between PEA and depression (r = –0.58; P < 0.01) was observed in the female subgroup. Furthermore, PEA correlated significantly negatively with hypochondriasis (r = –0.65; P < 0.01), paranoia (r = 0.49; P < 0.05), and social introversion (r = –0.60; P < 0.05). These results are the first evidence in normal individuals either that PEA itself might play a role in the modulation of affective behaviour, or alternatively that PEA could be related to mechanisms responsible for the modulation of affective behavior.     

Vasopressin in the cerebrospinal fluid of febrile children with or without seizures

Immaturity in water and electrolyte balance in the brain has been considered to increase the susceptibility of young animals and children to febrile convulsions (FCs). Arginine-vasopressin (AVP) is involved in the regulation of several centrally mediated events such as modulation of fever and the ease with which water permeates into and out of the brain. To evaluate the possible role of AVP in the control of water balance and susceptibility to convulsions during fever we measured the AVP concentration in the cerebrospinal fluid (CSF) and plasma of febrile children with or without convulsions. The febrile population consisted of 47 children, of whom 29 experienced seizures during fever. Seven children with epileptic symptoms and 18 children without seizures were included as nonfebrile controls. The CSF AVP concentration in febrile children without seizures and in nonfebrile convulsive children was significantly lower (0.60 ± 0.07 pmol / 1, mean ± SEM,P < 0.01 and 0.65 ± 0.19 pmol/l,P < 0.05, respectively) than in nonfebrile children without convulsions (0.83 ± 0.06 pmol/1). However, the levels of CSF AVP were not significantly different in children with FCs (0.71 ± 0.06 pmol/1) compared with other groups. CSF AVP correlated with the CSF osmolality (r = 0.33, P = 0.02). No statistical differences in plasma AVP levels between the groups could be found. The present data provide support for the hypothesis of synchronous regulation of osmolality and AVP concentration in CSF. During fever the concentration of CSF AVP was lower in nonconvulsive children compared with nonfebrile nonconvulsive children. CSF AVP levels were not affected in febrile children by convulsions.     

Intracerebroventricular infusion but not bolus injection of vasopressin increases the cerebrospinal fluid pressure in awake rabbits

The effect of intracerebroventricular infusion or injection of arginine vasopressin (AVP) was examined in awake rabbits with permanent ventricular cannulae. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) 43 μl min^–1 containing AVP concentrations exceeding 0.4 ng ml^–1, equivalent to an AVP infusion rate of 17.2 pg min^–1, caused a dose-dependent increase in intracranial pressure (ICP) of 3 to 5 mmHg after 30-50 min of AVP infusion. Intracerebroventricular bolus injection of equivalent doses of AVP did not provoke changes in ICP. At the end of the experiments cisternal CSF concentrations of AVP were higher after infusion of AVP than after injection of the same amount of AVP. The mean arterial blood pressure increased slightly in the group of animals infused with AVP at rates above 17.2 pg min^–1. It is concluded that intracerebroventricular infusion of AVP increases ICP in awake rabbits but the mechanism responsible for the elevation of ICP remains speculative.     

Non-invasive ICP monitoring in infants: the Rotterdam Teletransducer revisited

Measurement of intracranial pressure (ICP) is important in patients at risk of raised ICP, as in hydrocephalus. Ideally, it should be non-invasive, thus avoiding the risk of infection and other complications. Such is provided by measurement of ICP through the anterior fontanelle. There are several methods of measuring anterior fontanelle pressure (AFP); those most frequently used are based on the applanation principle. An evaluation of AFP measurement devices resulted in the choice of the Rotterdam Teletransducer (RTT) to be used in our study of children with hydrocephalus. The literature contains little information on the accuracy or validation of the AFP measurements using the RTT. Therefore, the physical qualities of the RTT were reassessed, using a specially developed calibration device. The results of this study demonstrate that membrane temperature does not have any effect on the measured pressure. The thermal stabilization time of the RTT was found to be 3 h after switching on . Insufficient thermal stabilization results in a pressure underestimation of up to 3 mmHg. Furthermore, a maximum inaccuracy of 2.6 mmHg, after calibration and readjustment of the transducer, was calculated. Validation of the equipment was achieved by simultaneous AFP/ICP measurements in hydrocephalic patients showing high correlations (r=0.96–0.98). The discusion suggests a measurement protocol as a means of increasing the reliability of RTT measurements.     

A randomized trial of very early decompressive craniectomy in children with traumatic brain injury and sustained intracranial hypertension

Object: The object of our study was to determine, in children with traumatic brain injury and sustained intracranial hypertension, whether very early decompressive craniectomy improves control of intracranial hypertension and long-term function and quality of life. Methods: All children were managed from admission onward according to a standardized protocol for head injury management. Children with raised intracranial pressure (ICP) were randomized to standardized management alone or standardized management plus cerebral decompression. A decompressive bitemporal craniectomy was performed at a median of 19.2 h (range 7.3–29.3 h) from the time of injury. ICP was recorded hourly via an intraventricular catheter. Compared with the ICP before randomization, the mean ICP was 3.69 mmHg lower in the 48 h after randomization in the control group, and 8.98 mmHg lower in the 48 hours after craniectomy in the decompression group (P=0.057). Outcome was assessed 6 months after injury using a modification of the Glasgow Outcome Score (GOS) and the Health State Utility Index (Mark 1). Two (14%) of the 14 children in the control group were normal or had a mild disability after 6 months, compared with 7 (54%) of the 13 children in the decompression group. Our conclusion was that when children with traumatic brain injury and sustained intracranial hypertension are treated with a combination of very early decompressive craniectomy and conventional medical management, it is more likely that ICP will be reduced, fewer episodes of intracranial hypertension will occur, and functional outcome and quality of life may be better than in children treated with medical management alone (P=0.046; owing to multiple significance testing P <0.0221 is required for statistical significance). This pilot study suggests that very early decompressive craniectomy may be indicated in the treatment of traumatic brain injury. Received: 5 May 2000 Revised: 2 September 2000     

Cerebral Glutamine Concentration and Lactate–Pyruvate Ratio in Patients with Acute Liver Failure

Aim  Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate–pyruvate ratio is associated with a rise in the glutamine concentration and ICP. Patients and Methods  In 13 patients with ALF (8F/5M; median age 46 (range 18–66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion pressure (CPP). Results  The cerebral glutamine concentration was 4,396 (1,011–9,712) μM, lactate 2.15 (1.1–4.45) mM, and pyruvate 101 (43–255) μM. The lactate–pyruvate ratio was 21 (16–40), ICP 20 (2–28) mmHg, and CPP 72 (56–115) mmHg. Cerebral glutamine concentration correlated with the lactate–pyruvate ratio (r = 0.89, P < 0.05). Also the ICP, but not CPP, correlated to the lactate–pyruvate ratio (r = 0.64, P < 0.05). Conclusion  ICP and the cerebral glutamine concentration in patients with ALF correlate to the lactate–pyruvate ratio. Since CPP was sufficient in all patients the rise in lactate–pyruvate ratio indicates that accumulation of glutamine compromises mitochondrial function and causes intracranial hypertension.     

The value of transcranial Doppler imaging in children with tuberculous meningitis

Purpose

Transcranial Doppler imaging (TCDI) is potentially a valuable investigational tool in children with tuberculous meningitis (TBM), a condition often complicated by pathology relevant to Doppler imaging such as raised intracranial pressure (ICP) and cerebral vasculopathies.

Methods

Serial TCDI was performed on 20 TBM children with the aim of investigating cerebrovascular haemodynamics and the relationship between pulsatility index (PI) and ICP.

Results

We observed a poor correlation between ICP and PI in children with communicating hydrocephalus (p?=?0.72). No decline in PI was noted following 7 days of medical therapy for communicating hydrocephalus (p?=?0.78) despite a concomitant decline in ICP. Conversely, a decline in PI was noted in all four children with non-communicating hydrocephalus who underwent cerebrospinal fluid diversion. High blood flow velocities (BFV) in all the basal cerebral arteries were observed in 14 children (70 %). The high BFV persisted for 7 days suggesting stenosis due to vasculitis rather than functional vasospasm. Complete middle cerebral artery (MCA) occlusion, subnormal mean MCA velocities (<40 cm/s) and PIs (<0.4) correlated with radiologically proven large cerebral infarcts.

Conclusions

TCDI-derived PI is not a reliable indicator of raised ICP in children with tuberculous hydrocephalus. This may be attributed to individual variation of tuberculous vascular disease, possibly compromising cerebral vascular compliance and resistance. Basal artery stenosis secondary to vasculitis is observed during the acute stage of TBM in the majority of children.     

Increased levels of plasma glial-derived neurotrophic factor in children with attention deficit hyperactivity disorder

Abstract

Background: Recent evidence suggests that neurotrophic growth factor systems, including brain-derived neurotrophic factor, might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Glial cell line-derived neurotrophic factor (GDNF) is from the transforming growth factor-β family and is abundantly expressed in the central nervous system, where it plays a role in the development and function of hippocampal cells. To date, no association studies have been done between ADHD and GDNF. Thus, here we investigate the hypothesis that there are differences in plasma GDNF levels between children with ADHD and healthy controls. Methods: Plasma GDNF levels were measured in 86 drug-naïve children with ADHD and 128 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in patients and healthy controls. Results: The median plasma GDNF levels in ADHD patients was 74.0 (IQR: 23.4–280.1) pg/ml versus 24.6 (IQR: 14.5–87.3) pg/ml in healthy controls; thus the median plasma GDNF levels in ADHD patients were significantly higher than in healthy controls (Mann–Whitney U-test, P < 0.01). Plasma GDNF levels were correlated positively with K-ARS subscale scores (inattention, hyperactivity–impulsivity and total), determined by Spearman's correlation test in ADHD patients and healthy controls (r = 0.371, P < 0.01; r = 0.331, P < 0.01; and r = 0.379, P < 0.01, respectively). Conclusions: These findings suggest increased plasma GDNF levels in untreated ADHD patients. In addition, plasma GDNF levels had a significant positive correlation with inattention, hyperactivity–impulsivity and K-ARS total scores in ADHD patients and healthy controls. Further studies are required to determine the source and role of circulating GDNF in ADHD.     

Cerebrovascular Pressure Reactivity and Cerebral Oxygen Regulation After Severe Head Injury

Background

To investigate the relationship between cerebrovascular pressure reactivity and cerebral oxygen regulation after head injury.

Methods

Continuous monitoring of the partial pressure of brain tissue oxygen (P_brO₂), mean arterial blood pressure (MAP), and intracranial pressure (ICP) in 11 patients. The cerebrovascular pressure reactivity index (PRx) was calculated as the moving correlation coefficient between MAP and ICP. For assessment of the cerebral oxygen regulation system a brain tissue oxygen response (TOR) was calculated, where the response of P_brO₂ to an increase of the arterial oxygen through ventilation with 100 % oxygen for 15 min is tested. Arterial blood gas analysis was performed before and after changing ventilator settings.

Results

Arterial oxygen increased from 108 ± 6 mmHg to 494 ± 68 mmHg during ventilation with 100 % oxygen. P_brO₂ increased from 28 ± 7 mmHg to 78 ± 29 mmHg, resulting in a mean TOR of 0.48 ± 0.24. Mean PRx was 0.05 ± 0.22. The correlation between PRx and TOR was r = 0.69, P = 0.019. The correlation of PRx and TOR with the Glasgow outcome scale at 6 months was r = 0.47, P = 0.142; and r = ?0.33, P = 0.32, respectively.

Conclusions

The results suggest a strong link between cerebrovascular pressure reactivity and the brain’s ability to control for its extracellular oxygen content. Their simultaneous impairment indicates that their common actuating element for cerebral blood flow control, the cerebral resistance vessels, are equally impaired in their ability to regulate for MAP fluctuations and changes in brain oxygen.     

Vasopressin and the regulation of evaporative water loss and body temperature in the cat

The role of vasopressin as a possible mediator of the inhibition of evaporative water loss (EWL) in dehydrated, heat-stressed cats has been examined by intravenous (i.v.) and intracerebroventricular (i.c.v.) injections of arginine vasopressin (AVP). In normally hydrated cats exposed to an ambient temperature (Ta) of 38°C, neither EWL nor body temperature (Tb), measured in the hypothalamus, was significantly altered by i.v. AVP infusion. Measurements of plasma osmolality (pOsm), pAVP and cerebrospinal fluid AVP (csfAVP) were made normally hydrated cats at Tas of 25 and 38°C and after dehydration for 1–4 days at these temperatures. The relationship between pOsm and pAVP can be described equally well by either a linear model or a log-linear model (r = 0.81 for both models). The pOsm-csfAVP relationship is best described by alog-linear model (r = 0.80). A possible role for intracranially released AVP in ody temperature regulation and control of EWL was examined by injecting various doses of AVP into the lateral ventricles of normally hydrated cats. No effect of AVP injection on Tb was observed at either a Ta of 23°C or 38°C. EWL was also unaffected by i.c.v. AVP administration at a Ta of 38°C. To confirm futher that intracranial AVP is not responsible for elevation of Tb and reduction of EWL during dehydration and heat-stress, specific antiserum to AVP was injected into the ventricle of dehydrated animals at a Ta of 38°C. No sinificant effect on either Tb or EWL was measured subsequent to antiserum infusion. These negative findings indicate that AVP does not suppress EWL by either a peripheral or a central action and is therefore not responsible for lowered EWL and elevated Tb seen in dehydrated heat-stressed cats.     

Evaluation of intracranial pressure from transcranial Doppler studies in cerebral disease

Summary The extent to which estimations of intracranial pressure can be derived from intracranial flow patterns was studied. The blood flow velocity in the middle cerebral artery was recorded with the EME TC 2–64 transcranial Doppler (TCD) device in 26 patients suffering from various severe cerebral diseases. Simultaneously the mean intracranial pressure (ICP) was measured by means of an epidural device. Arterial carbon-dioxide tensions were monitored by blood gas analysis. In all patients it was observed that the middle cerebral artery flow patterns changed distinctly when the ICP increased; these changes were distinguished by a decrease of the mean flow velocity and an increase of the Pourcelot index. A good correlation between the ICP and the flow parameters (especially the product mean systemic arterial pressure × Pourcelot index/mean flow velocity) was found in a select group of 13 patients, in whom comparable initial conditions existed and in whom additional parameters influencing the TCD recordings could be kept constant (r=0.873; P<0.001).Supported by the Deutsche Forschungsgemeinschaft (SFB 330 — Organprotektion)     

Age-related differences in intracranial pressure and cerebral perfusion pressure in the first 6 hours of monitoring after children’s head injury: association with outcome

Objectives Severe head injury in childhood is associated with considerable mortality and morbidity. In this study we determined age-related differences in the relationship between outcome and intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in the first 6 h of monitoring in a large cohort of head-injured children.Methods Two hundred and thirty-five head-injured children (admitted to five UK hospitals over a 15-year period) in whom intracranial pressure monitoring was clinically indicated were studied.Results Patients were divided into three age groups (2–6, 7–10 and 11–16 years). The sensitivity of ICP and CPP were similar. Differences were found in the specificity of ICP and CPP for each group and these were more marked for CPP. For a specificity of 50% the pressures were 53, 63 and 66 mmHg for the three age groups.Conclusions There are age-related differences in the specificity of intracranial pressure and cerebral perfusion pressure in relation to outcome. These differences may be important in the clinical management of head-injured children. Thus cerebral perfusion pressures of 53, 63 and 66 mmHg should be the minimum to strive for in these three age groups respectively.     

Continuous low dose diclofenac sodium infusion to control fever in neurosurgical critical care

Introduction  Aim of this randomized prospective clinical trial is to compare two methods of antipyretics and evaluate their efficacy in controlling fever during the acute phase of brain damage. Methods  Twenty-two febrile comatose patients: 12 severe traumatic brain injury and 10 subarachnoid hemorrhage divided in 2 groups: Diclofenac low-dose infusion (10 patients) and extemporaneous boluses of NSAIDs (CTRL, 12 patients). The primary outcome measure was length of time with temperature >38°C. Secondary outcome measures were: 1) to assess the effects of each antipyretic strategy on intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP) and heart rate; 2) to monitor adverse effects of each antipyretic strategy. The baseline characteristics in the two treatment groups were similar. Results  Primary findings: percentage of time per patient with temperature >38°C was significantly lower (P < 0.0001) in the DCF group, 4% (0–22%), vs. 34% (8–56%) in CTRL group. In addition, mean T°, max T° were lower in DCF than in CTRL (P < 0.05). Secondary findings: CPP and MAP were significantly higher in DCF group (P < 0.05) while ICP was not different (NS). However, if ICP pre randomization was < 25 mmHg, CTRL suffered a worst ICP (24 ± 11 vs. 16 ± 7 P = 0.01), MAP (89 ± 10 vs. 104 ± 10 P = 0.01) and CPP (75 ± 10 vs. 94 ± 17 P = 0.01) compared to DCF. No differences between the two treatment were recorded when ICP ≥ 25 mmHg before randomization. There was no gastrointestinal or intracranial bleeding. Conclusions  Low dose DCF infusion is a potential useful strategy for a successful control temperature better than intermittent NSAIDs dosing, minimizing potentially brain-damaging effects of fever.     

Cerebral critical closing pressure in hydrocephalus patients undertaking infusion tests

Abstract

Objectives:

Links between cerebrospinal fluid (CSF) compensation and cerebral blood flow (CBF) have been studied in many clinical scenarios. In hydrocephalus, disturbed CSF circulation seems to be a primary problem, having been linked to CBF disturbances, particularly in white matter close to surface of dilated ventricles. We studied possible correlations between cerebral haemodynamic indices using transcranial Doppler (TCD) ultrasonography and CSF compensatory dynamics assessed during infusion tests.

Methods:

We analysed clinical data from infusion tests performed in 34 patients suspected to suffer from normal pressure hydrocephalus, with signals including intracranial pressure (ICP), arterial blood pressure (ABP) and TCD blood flow velocity (FV). Cerebrospinal fluid compensatory parameters (including elasticity) were calculated according to a hydrodynamic model of the CSF circulation. Critical closing pressure (CrCP) was calculated with the cerebrovascular impedance methodology, while wall tension (WT) was estimated as CrCP-ICP. Closing margin (CM) was expressed as the difference between ABP and CrCP.

Results:

Intracranial pressure increased during infusion from 6.7?±?4.6 to 25.0?±?10.5?mmHg (mean?±?SD; P?<?0.001), resulting in CrCP rising by 22.9% (P?<?0.001) and WT decreasing by 11.3% (P?=?0.005). Closing margin showed a tendency to decrease, albeit not significantly (P?=?0.070) due to rising ABP (9.1%; P?=?0.005). Closing margin at baseline ICP was inversely correlated to brain elasticity (R?=?(0.358; P?=?0.038), while being significantly different from zero for the whole duration of the tests (52.8?±?22.8?mmHg; P?<?0.001). Neither CrCP nor WT was correlated with CSF compensatory parameters.

Discussion:

Critical closing pressure increases and WT decreases during infusion tests. Closing margin at baseline pressure may act as an indicator of the cerebrospinal compensatory reserve.     

Phaeochromocytoma: Intraoperative changes in blood pressure and plasma catecholamines

The aim of this study was to assess the relationship between changes in plasma catecholamine concentrations and intraarterial blood pressure (BP) measured simultaneously during resection of phaeochromocytoma (n = 14). Arterial plasma concentrations of noradrenaline (NA), adrenaline (A) and dopamine (DA) were measured by a radio-enzymatic method. Arterial NA concentrations (pmol/ml; median and Wilcoxon 95% CI) were 71.8 (46,162) before induction of anaesthesia, 113.0 (79,231) after intubation, 375.0 (285,931) during tumour handling and 32.5 (18,88) following tumour removal. Simultaneous mean BP values (mmHg; Mean ± SEM) were 119 ± 8, 114 ± 7, 159 ± 7 (p = 0.0001) and 72 ± 6 (p < 0.0001) respectively. At the time of tumour handling there was a weak correlation between plasma NA and A combined and mean BP (r = 0.583,p = 0.029) and a stronger correlation between log plasma NA and A combined and pulse pressure (r = 0.749,p = 0.008). The very large rises in plasma catecholamine concentrations and in BP are likely to have been causally related. Individual patients maintained a constant ratio of NA to A in plasma from pre-induction to tumour handling (r = 0.916,p < 0.0001). The maintenance of a constant NA: A ratio suggests that the pattern of catecholamine synthesis and release may be a characteristic of the individual tumour.     

Polynitroxylated-pegylated hemoglobin attenuates fluid requirements and brain edema in combined traumatic brain injury plus hemorrhagic shock in mice

Polynitroxylated-pegylated hemoglobin (PNPH), a bovine hemoglobin decorated with nitroxide and polyethylene glycol moieties, showed neuroprotection vs. lactated Ringer''s (LR) in experimental traumatic brain injury plus hemorrhagic shock (TBI+HS). Hypothesis: Resuscitation with PNPH will reduce intracranial pressure (ICP) and brain edema and improve cerebral perfusion pressure (CPP) vs. LR in experimental TBI+HS. C57/BL6 mice (n=20) underwent controlled cortical impact followed by severe HS to mean arterial pressure (MAP) of 25 to 27 mm Hg for 35 minutes. Mice (n=10/group) were then resuscitated with a 20 mL/kg bolus of 4% PNPH or LR followed by 10 mL/kg boluses targeting MAP>70 mm Hg for 90 minutes. Shed blood was then reinfused. Intracranial pressure was monitored. Mice were killed and %brain water (%BW) was measured (wet/dry weight). Mice resuscitated with PNPH vs. LR required less fluid (26.0±0.0 vs. 167.0±10.7 mL/kg, P<0.001) and had a higher MAP (79.4±0.40 vs. 59.7±0.83 mm Hg, P<0.001). The PNPH-treated mice required only 20 mL/kg while LR-resuscitated mice required multiple boluses. The PNPH-treated mice had a lower peak ICP (14.5±0.97 vs. 19.7±1.12 mm Hg, P=0.002), higher CPP during resuscitation (69.2±0.46 vs. 45.5±0.68 mm Hg, P<0.001), and lower %BW vs. LR (80.3±0.12 vs. 80.9±0.12%, P=0.003). After TBI+HS, resuscitation with PNPH lowers fluid requirements, improves ICP and CPP, and reduces brain edema vs. LR, supporting its development.