Elevations of neuropeptide Y-like immunoreactivity and catecholamines in plasma on increased intracranial pressure in the pig

Graded increases of intracranial pressure (ICP) in anaesthetized pigs induced elevations of plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and catecholamines, simultaneously with hypertension and tachycardia. Plasma adrenaline (ADR) increased at a lower ICP-level than did the plasma levels of noradrenaline (NA) and NPY-LI. At the maximal ICP elevation, 22.9 kPa (172 mmHg), plasma NPY-LI was increased about 10-fold, from 48 +/- 8 pmol/l in the basal state, while NA and ADR concentrations increased more than 100-fold. At this maximal ICP-level the plasma levels of NPY-LI were correlated to the concentrations of both NA (r = 0.87, P less than 0.01) and ADR (r = 0.92, P less than 0.001). Plasma NPY-LI continued to increase to about 1000 pmol/l, 10 min after the maximal elevation of ICP was discontinued, while the catecholamines then had declined considerably. A slight cardiac release of NPY-LI was observed at the maximal elevation of ICP. The half-life of NPY-LI in plasma was about 6 min upon systemic infusion. At plasma levels similar to those obtained upon maximal ICP elevation, exogenous NPY caused slight vasoconstriction in the spleen and skeletal muscle, but had no effects on coronary blood flow or systemic blood pressure. This suggests that NPY mainly exerts local actions after release from nerve endings, while levels of circulating NPY in plasma must be very high to influence blood flow in some organs. It is concluded that elevation of ICP results in hypertension and tachycardia related to elevated plasma levels of NPY-LI and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of indomethacin on intracranial pressure,cerebral blood flow and cerebral metabolism in patients with severe head injury and intracranial hypertension

Summary In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control intracranial pressure (ICP) (ICP>20 mmHg) by artificial hyperventilation (PaCO₂ level 3.5–4.0 kPa) and barbiturate sedation, indomethacin was used as a vasoconstrictor drug. In all patients, indomethacin (a bolus injection of 30 mg, followed by 30 mg/h for seven hours) reduced ICP below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in CBF at 2h. After 7h, ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In the other patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. These results suggest that indomethacin due to its cerebral vasoconstrictor and antipyretic effect should be considered as an alternative for treatment of ICP-hypertension in head-injured patients.Presented at the Fifth Nordic CBF Symposium, Lund, Sweden, 21–22 May 1990.     

Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury – a study of cerebral blood flow and metabolism

Summary Objective. To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO₂), glucose (CMRGlc) and lactate (CMRLct). Methods. Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO₂ from 36 ± 4 to 32 ± 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO₂, CMRGlc and CMRLct. Results. Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml·100 gr⁻¹·min⁻¹ were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO₂, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. Conclusions. Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.     

A porcine model for evaluation of cerebral haemodynamics and metabolism during increased intracranial pressure

In patients with severe head injuries raised intracranial pressure (ICP) constitutes the most important cause of mortality. Several new therapies for increased ICP have recently been suggested and it is of importance to study the physiological effects of these treatments in animal experiments during steady state conditions. A porcine model for evaluation of cerebral haemodynamics and metabolism during increased ICP is presented. Intracranial hypertension was induced by inflation of two tonometric gastric balloons placed extradurally covering a major part of the parietooccipital region bilaterally. The distribution of the blood flow supplied by the carotid artery used for the cerebral blood flow (CBF) measurements was studied by intraarlerial (i.a.) injection of ^99mTc-HMPAO.
The measurements showed that following ligation of the external carotid and the occipital artery no accumulation of tracer substance occurred in extracranial tissues during normal or increased ICP. Cerebral physiological variables (CBF, Cavo₂, and ICP) were measured 5, 20 and 60 rnin after induction of intracranial hypertension. The results confirm that the experimental situation gives a reproducible increase in ICP (25–28 mm Hg) and that the physiological variables remain stable during the period of intracranial hypertension. We conclude that the model simulates the effects of an acute intracranial focal mass and is well suited for the evaluation of different pharmacological therapies of increased ICP.     

Haemodynamic,intracranial pressure and electrocardiographic changes following subarachnoid haemorrhage in rats

Summary Experimental induction of subarachnoid haemorrhage in rats resulted in acute haemodynamic changes. Heart rate decreased concomitantly with a rise in arterial blood pressure. Intracranial pressure increased and consequently cerebral perfusion pressure dropped. These changes as well as the observed electrocardiographic (ECG) changes were comparable to those reported in patients. Apart from blood also saline, when introduced into the cisterna magna, was able to elicit such abnormalities. The haemodynamic and electrocardiographic changes, which result from subarachnoid haemorrhage, may even become aggravated, when repetitive injections of blood or saline are given into the cisterna magna and when cerebral angiography is performed prior to induction of the subarachnoid haemorrhage. Chronic intracranial pressure monitoring during the 48 hours following subarachnoid haemorrhage revealed no significant rise in pressure.A thorough control of the experimental conditions is thus of utmost importance in order to give a valid interpretation of the observed anomalies.     

Effect of remifentanil on intracranial pressure and cerebral blood flow velocity in patients with head trauma

BACKGROUND: Remifentanil, an ultra-short-acting opioid, is used as an on-top analgesic in head trauma patients during transient painful procedures, e.g. endotracheal suctioning, physiotherapy, on the intensive care unit. However, previous studies have shown that opioids may increase intracranial pressure and decrease cerebral blood flow. METHODS: The present study investigates the effect of remifentanil on mean arterial blood pressure, intracranial pressure measured with intraparenchymal or epidural probes, and on cerebral blood flow velocity assessed by transcranial Doppler flowmetry in 20 head trauma patients sedated with propofol and sufentanil. Ventilation was adjusted for a target PaCO2 of 4.7-5.1 kPa. After baseline measurements a bolus of remifentanil (0.5 microg x kg(-1) i.v.) was administrated followed by a continuous infusion of remifentanil (0.25 microg x kg(-1) x min(-1) i.v.) for 20 min. RESULTS: There was no change in mean arterial blood pressure, intracranial pressure, and cerebral blood flow velocity in response to remifentanil infusion over time. Statistical analysis was performed using the Wilcoxon Signed Rank test. CONCLUSIONS: These data suggest that remifentanil can be used for on-top analgesia in head trauma patients without adverse effects on cerebrovascular haemodynamics, cerebral perfusion pressure or intracranial pressure.     

Effects of sevoflurane on intracranial pressure, cerebral blood flow and cerebral metabolism: A dose-response study in patients subjected to craniotomy for cerebral tumours

Background: Studies concerning the cerebrovascular effects of sevoflurane in patients with space-occupying lesions are few. This study was carried out as a dose-response study comparing the effects of increasing sevoflurane concentration (1.5% (0.7 MAC) to 2.5% (1.3 MAC)) on cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular resistance (CVR), metabolic rate of oxygen (CMRO₂) and CO₂-reactivity in patients subjected to craniotomy for supratentorial brain tumours.
Methods: Anaesthesia was induced with propofol/fentanyl/atracurium and maintained with 1.5% sevoflurane in air/oxygen at normocapnia. Blood pressure was maintained constant by ephedrine. In group 1 (n=10), the patients received continuously 1.5% sevoflurane. Subdural ICP, CBF and CMRO₂ were measured twice at 30-min intervals. In group 2 (n=10), sevoflurane concentration was increased from 1.5% to 2.5% after CBF₁. CBF₂ was measured after 20 min during 2.5% sevoflurane. Finally, CO₂-reactivity was studied in both groups.
Results: In group 1, no time-dependent alterations in CBF, CVR, ICP and CMRO₂ were found. In group 2, an increase in sevoflurane from 1.5% to 2.5% resulted in an increase in CBF from 29 ± 10 to 34±12 ml 100g⁻¹ min⁻¹ and a decrease in CVR from 2.7±0.9 to 2.3±1.2 mmHg ml⁻¹ min 100g ( P <0.05), while ICP and CMRO₂ were unchanged. CO₂-reactivity was maintained at 1.5% and 2.5% sevoflurane.
Conclusion: Sevoflurane is a cerebral vasodilator in patients with cerebral tumours. Sevoflurane increases CBF and decreases CVR in a dose-dependent manner. CO₂-reactivity is preserved during 1.5% and 2.5% sevoflurane.     

Somatosensory evoked potentials and intracranial pressure during chronic dilatation of an artificial extraparenchymal space-occupying lesion in cats

Summary Somatosensory evoked potentials (SEP) and intracranial pressure (ICP) were studied in cats, suffering from a chronic spaceoccupying lesion produced by enlargement of an epidural balloon over the left sensomotory cortex. Our study shows that latency alterations of SEP are not dependent on the degree of ICP. Additionally, the results obtained demonstrate that chronic space-occupying lesions cause continuous prolongation of SEP latencies, probably produced by atrophy of the compressed tissue. Regarding the clinical importance of SEP measurements, we concluded that they are not suitable for estimating the degree of ICP. However, they are useful to evaluate tissue damage caused by mass effects in the acute and chronic phase of various space-occupying processes.This work was supported in part by the Deutsche Forschungsgemeinschaft, grant Bo 920/1-2.     

呼气末正压对不同血容量状态猪颅高压模型颅内压和脑氧代谢影响的实验研究

目的:观察不同血容量状态下颅高压的急性呼吸窘迫综合征(ARDS)猪模型,增加呼气末正压(PEEP)后,其血流动力学状态、颅内压(ICP)及脑氧分压(PtiO 2)的变化。 方法:选取雄性14～16月龄巴马小型猪12头,随机数字表法随机分成低血容量组和正常血容量组。建立ARDS和颅高压模型。自5 c...     

Effect of increased intraabdominal pressure on cardiac output and tissue blood flow assessed by color-labeled microspheres in the pig

apd: 12 December 2000     

Quantitative cerebral blood flow and metabolism determination in the first 48 hours after severe head injury with a new dynamic spect device

SummaryObjective To determine cerebral blood flow (CBF) and metabolism in the acute phase after severe head injury by a new dynamic SPECT device using¹³³Xenon and to evaluate a possible role of CBF and metabolism in the determination of prognosis.Design Prospective studySetting General intensive care unit in a universitary teaching hospitalSubjects 23 severely head injured patients having CT scan and CBF determination, intracranial pressure (ICP) and jugular bulb oxygen saturation monitoring in the first 48 hours.Measurements and main results CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found between early CBF and severity of trauma evaluated with the Glasgow Coma Score (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated with Glasgow outcome score (GOS) (F = 0.491, p = 0.622; r_s = 0.251, p = 0.246). CMRO₂ was depressed in relation to the severity of injury, specifically ranging from 0.9±0.5 ml/ 100 g/min in patients with GCS 3 to 1.7 ±0.8 ml/100 g/min in patients with GCS 6–7. In no patient with a CMRO₂ less than 0.8 ml/100 g/min was a good outcome observed. A significant correlation was found between GCS and GOS (r_s = 0.699, p = 0.0002), between CMRO₂ and GOS (F = 4.303, p = 0.031; r_s = 0.525, p = 0.013) and between AJDO₂ and GOS (F = 3.602, p = 0.046; r_s = 0.491, p = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly lower than normal values (²=18.658, p = 0.001) but did not correlate either with prognosis (² = 1.626, p = 0.443) or with severity (² = 1.913, p = 0.384).Conclusions CBF in the first 48 hours after trauma varies within a large range of values and is not correlated with severity and prognosis. Clinical evaluation with GCS and CMRO₂ are much more reliable indicators of severity of head trauma and have a significant role in the determination of prognosis. F/O ration is significantly altered from normal values confirming post-traumatic hypofrontalism but does not correlate with severity and prognosis.     

Racemic, S(+)- and R(-)-ketamine do not increase elevated intracranial pressure

Background: There is controversy regarding the influence of ketamine and its enantiomers on cerebral haemodynamics at increased intracranial pressure (ICP). This study was designed to compare cerebrovascular responses, with particular respect to ICP, to bolus injections of racemic, S(+)- and R(−)-ketamine in an experimental model of intracranial hypertension.
Methods: Nine pigs were anaesthetised with fentanyl and vecuronium during mechanical normoventilation. The ICP was raised with extradural balloon catheters to 23 mmHg. The intra-arterial xenon clearance technique was used to determine cerebral blood flow (CBF). Three 60-s bolus injections of racemic ketamine (10 mg/kg), S-ketamine (5 mg/kg) and R-ketamine (20 mg/kg) were given in a randomised sequence. Cerebral and systemic haemodynamic responses were evaluated before and at 1, 5, 10, 15, 30 and 45 min after each injection.
Results: Racemic ketamine decreased ICP ( P =0.026) by maximally 10.8%, whereas there was no effect on ICP of S- ( P =0.178) or R-ketamine ( P =0.15). All study drugs had similar biphasic effects on CBF, with maximal initial decreases by 25–29%, followed by transient increases by 7–15%, and a reduction of mean arterial pressure by maximally 22–37%.
Conclusions: A decrease or a lack of an increase in ICP in response to intravenous bolus injections of racemic, S- or R-ketamine suggests that the administration of racemic or S-ketamine might be safe in patients with intracranial hypertension due to a space-occupying lesion. The ICP-lowering effect indicates that racemic ketamine might offer a therapeutic advantage over S-ketamine.     

颅内肿瘤手术麻醉期间颅内压和脑脊液pH的临床研究

目的 通过颅内肿瘤手术麻醉期间颅内压（ＩＣＰ）和脑脊液ｐＨ值（ＣＳＦｐＨ）的对比观察,探索术中对ＩＣＰ的调控措施。方法 随机选择颅内肿瘤择期手术病人４５例。全部病人在安定、芬太尼、２％硫喷妥钠、阿曲库铵麻醉下实施肿瘤切除术,于麻醉前、麻醉后、切开硬膜、切除瘤体、手术毕、拔管后不同时间测定ＩＣＰ和ＣＳＦｐＨ值。结果 与麻醉前相比,麻醉后ＩＣＰ逐渐升高,ＣＳＦｐＨ麻醉后逐渐降低（Ｐ〈０．０１）。打开颅     

Increased intracranial pressure and cardiac arrest after heart transplantation. What about the Cushing response in a denervated heart? Case report

A 13-year-old boy suffered cerebrovascular complications after heart transplantation (ischemic mass effect in the posterior cranial fossa). He had to be resuscitated from cardiac arrest with coma. After a modified cerebellar hemispherectomy the course was favorable.—The most conclusive explanation for the acute event is that a Cushing response was preserved even in the presumably denervated heart.     

Cerebral blood flow and glucose metabolism in the squirrel monkey during the late phase of cerebral vasospasm

Summary A double-isotope autoradiography technique was used to evaluate cerebral blood flow (CBF) and cerebral glucose metabolism (CMRglu) during the late phase of vasospasm in a squirrel monkey subarachnoid haemorrhage (SAH) model. Cisternal blood injections induced both global and focal changes in CBF and CMRglu six days following SAH, the timepoint of maximal late spasm in this model. There was a global decrease in CBF of about 30% accompanied by an increase in deoxyglucose uptake of about 50%. Four of seven animals also had foci with flow decreased to 40% of control and deoxyglucose uptake increased to 300% of control. There was an altered but still present interdependence between flow and metabolism post SAH.     

Coupling of function,metabolism, and blood flow in the brain

Functional activity, metabolism and blood flow are locally heterogeneous in the brain, but tightly coupled. This adjustment occurs in two different ways: 1. Shortterm, dynamic coupling mediated by local vasoactive factors that ensure second-to-second regulation. 2. Long-term, static coupling apparently mediated by capillary density and developed in response to local functional and metabolic activity. Recognizing these two mechanisms permits one to distinguish apparent from real uncoupling. It allows the conclusion that there is no indication of an uncoupling of metabolism and blood flow during physiological conditions.     

The effects of an extradural expanding lesion on regional intracranial pressure,blood flow,somatosensory conduction and brain herniation: an experimental study in baboons

Summary Intracranial pressure (ICP) differences, change of local blood flow (CBF) using the hydrogen clearance technique, change in the somatosensory evoked potential (SEP) to median nerve stimulation and pupillary size were investigated during progressive elevation of the ICP (using an extradural balloon) in 6 anaesthetized baboons. CBF was measured in the frontal cortex, somatosensory cortex, thalamus (nucleus ventralis posterior lateralis—VPL), medial lemniscus (ML), lateral lemniscus (LL) and caudate nucleus (CN). Conduction along the somatosensory pathway between C 2 at the neck and VPL was compared with conduction between VPL and primary somatosensory cortex. The amplitude of the cortical SEP was also studied.ICP gradients between hemispheres developed as the pressure was increased to in excess of 50 mm Hg. CBF was significantly reduced from control in the cortex and VPL on the side ipsilateral to the balloon at 50 mm Hg ICP. A significant decrease in ML flow occurred bilaterally at 70 mm Hg ICP. Conduction time was increased significantly between the right VPL and cortex at a pressure of 50 mm Hg. The amplitude of the cortical response was significantly reduced at 30 mm Hg on the right side and 50 mm Hg on the left. Aniscoria occurred at 50 mm Hg ICP and the pupils became dilated at 70 mm Hg. The SEP was possibly more sensitive than the pupillary reactions as an indication of tentorial herniation in these experiments.     

Comparative study of the microvascular blood flow in the intestinal wall during conventional negative pressure wound therapy and negative pressure wound therapy using paraffin gauze over the intestines in laparostomy

Higher closure rates of the open abdomen have been reported with negative pressure wound therapy (NPWT) than with other kinds of wound management. We have recently shown that NPWT decreases the blood flow in the intestinal wall, and that the blood flow could be restored by inserting a protective disc over the intestines. The aim of the present study was to investigate whether layers of Jelonet? (Smith & Nephew) dressing (paraffin tulle gras dressing made from open weave gauze) over the intestines could protect the intestines from hypoperfusion. Midline incisions were made in ten pigs and were subjected to treatment with NPWT with and without four layers of Jelonet over the intestines. The microvascular blood flow was measured in the intestinal wall before and after the application of topical negative pressures of ?50, ?70 and ?120 mmHg, using laser Doppler velocimetry. Baseline blood flow was defined as 100% in all settings. The blood flow was significantly reduced, to 61 ± 7% (P < 0·001), after the application of ?50 mmHg using conventional NPWT, and to 62 ± 7% (P < 0·001) after the application of ?50 mmHg with Jelonet dressings between the dressing and the intestines. The blood flow was significantly reduced, to 38 ± 5% (P < 0·001), after the application of ?70 mmHg, and to 42 ± 6% (P < 0·001) after the application of ?70 mmHg with Jelonet dressings. The blood flow was significantly reduced, to 34 ± 9% (P < 0·001), after the application of ?120 mmHg, and to 38 ± 6% (P < 0·001) after the application of ?120 mmHg with Jelonet dressings. The use of four layers of Jelonet over the intestines during NPWT did not prevent a decrease in microvascular blood flow in the intestinal wall.     

Effects of increases in the inspired oxygen fraction on brain surface oxygen pressure fields in pig and man

In six patients undergoing neurosurgical operation, brain surface oxygen pressure was studied during an increase of the inspired oxygen fraction (FiO2). The eight-channel oxygen surface electrode (MDO-electrode) was placed directly on the brain cortex. FiO2 was increased to four levels, from baseline level 0.21 to 0.3, 0.5, 0.7 and 1.0, respectively. During these four stages and FiO2 0.21, brain surface oxygen pressure (PtO2) was measured. The physiological variables such as blood pressure, PaCO2, pH and temperature were stable throughout the study. The results are presented as mean values +/- s.d. and a PtO2 histogram for each FiO2-level. Already at an FiO2 of 0.3 (at a PaO2 of 16.3 +/- 3.4 kPa) scattered histograms were seen in five of six patients. A scattered histogram indicates disturbed microcirculation. At the FiO2 levels of 0.5, 0.7 and 1.0, all histograms were scattered. The PtO2 values did not increase proportionally to PaO2 at FiO2 levels 0.3, 0.5 or 0.7. But at FiO2 1.0 four patients had normal mean PtO2 values and two patients very high mean PtO2 values. It is possible that the four patients with normal PtO2 values succeeded in regulating the cerebral microcirculation as a response to the high FiO2 leading to a high PaO2 (60.1 +/- 6.4 kPa). The same study was initially done on six pigs in which the regional cerebral blood flow (rCBF) was also measured. MDO-electrode measurements at different FiO2-levels gave the same results as in the patients. rCBF decreased when FiO2 was increased.