Continuous cerebral compliance monitoring in severe head injury: its relationship with intracranial pressure and cerebral perfusion pressure

Summary Background. Cerebral compliance expresses the capability to buffer an intracranial volume increase while avoiding a rise in intracranial pressure (ICP). The autoregulatory response to Cerebral Perfusion Pressure (CPP) variation influences cerebral blood volume which is an important determinant of compliance. The direction of compliance change in relation to CPP variation is still under debate. The aim of the study was to investigate the relationship between CPP and compliance in traumatic brain injured (TBI) patients by a new method for continuous monitoring of intracranial compliance as used in neuro-intensive care (NICU).Method. Three European NICU’s standardised collection of CPP, compliance and ICP data to a joint database. Data were analyzed using an unpaired student t-test and a multi-level statistical model.Results. For each variable 108,263 minutes of data were recorded from 21 TBI patients (19 patients GCS≤8; 90% male; age 10–77 y). The average value for the following parameters were: ICP 15.1±8.9 mmHg, CPP 74.3±14 mmHg and compliance 0.68±0.3 ml/mmHg. ICP was ≥20 mmHg in 20% and CPP<60 mmHg for 10.7% of the time. Compliance was lower (0.51±0.34 ml/mmHg) at ICP≥20 than at ICP<20 mmHg (0.73±0.37 ml/mmHg) (p<0.0001). Compliance was significantly lower at CPP<60 than at CPP≥60 mmHg: 0.56±0.36 and 0.70±0.37 ml/mmHg respectively (p<0.0001). The CPP – compliance relationship was different when ICP was above 20 mmHg compared with below 20 mmHg. At ICP<20 mmHg compliance rose as CPP rose. At ICP≥20 mmHg, the relation curve was convexly shaped. At low CPP, the compliance was between 0.20 and 0.30 ml/mmHg. As the CPP reach 80 mmHg average compliance was 0.55 ml/mmHg., but compliance fell to 0.40 ml/mmHg when CPP was 100 mmHg.Conclusions. Low CPP levels are confirmed to be detrimental for intracranial compliance. Moreover, when ICP was pathological, indicating unstable intracranial equilibrium, a high CPP level was also associated with a low volume-buffering capacity.     

Could B-type Natriuretic Peptide (BNP) plasma concentration be useful to predict fluid in critically ill patients with acute circulatory failure?

Background and objectives

As B-type Natriuretic Peptide (BNP) is a marker of ventricular wall stress, the present study was aimed at determining whether plasma BNP concentration could predict fluid responsiveness in critically ill patients with acute circulatory failure.

Methods

This prospective and non randomized interventional study included 33 sedated, mechanically ventilated patients, with acute circulatory failure requiring cardiac output measurement and fluid challenge. Plasma BNP concentration was measured before and after fluid challenge (250 to 500 ml with infusion rate = 999 ml/h). An increase in stroke index (SI) greater than or equal to 15% allowed separation of responders from nonresponders. Receiver operating characteristic (ROC) curves were generated for BNP and compared to that of central venous pressure (CVP) that is routinely considered as a marker of cardiac preload.

Results

Among 33 patients, there were 24 responders. At baseline, BNP plasma values were less in responders (328 [35–1190] pg/ml versus 535 [223–5000] pg/ml, p < 0.03). The area under the ROC curves was 0.74 ± 0.11, that was similar to the area under the ROC curve for CVP (0.77 ± 0.10). The best cut-off value of plasma BNP level for predicting fluid responsiveness was 193 pg/ml (sensitivity: 38%, specificity: 100%, positive predictive value: 100%, negative predictive value: 38%, accuracy: 55%). Fluid challenge did not increase plasma BNP concentrations in responders and nonresponders.

Conclusion

In critically ill patients with acute circulatory failure, BNP does not accurately predict fluid responsiveness.     

Endoluminal pelvic perfusion with norepinephrine causes only minor systemic effects and diminishes the increase in pelvic pressure caused by perfusion

OBJECTIVE: To evaluate the effect of endoluminal norepinephrine (NE) on transport pressures of the normal upper urinary tract of the pig and on plasma levels of NE in relation to possible systemic effects. MATERIAL AND METHODS: Six anaesthetized pigs weighing approximately 39 kg were studied. Transparenchymally, two 6-F catheters were introduced into the renal pelvis bilaterally to measure pressure and perfusion. Ultrasonic flow probes recorded renal arterial blood flow, and a transurethral 10-F catheter drained the bladder and monitored diuresis. In all six animals, the bilateral pelvic pressure response was examined at increasing perfusion rates (2, 4, 6, 8, 10 and 15 ml/min) and with increasing doses of NE (0, 5, 50 and 100 microg/ml). Arterial blood samples were analysed for NE, epinephrine and blood glucose. The systemic blood pressure, heart rate and electrocardiogram were registered. RESULTS: At all the investigated concentrations, endoluminal NE significantly diminished the increase in pelvic pressure caused by pelvic perfusion at all flow rates. At the lowest concentration of NE, no significant increase in the plasma level of NE was observed and the blood pressure did not increase. During perfusion with 50 and 100 microg/ml NE, plasma levels of NE increased significantly from 487+/-398 to 1798+/-910 and 2961+/-2093 pg/ml, respectively. This was accompanied by significant rises in mean systolic blood pressure from a baseline value of 95+/-10 mmHg to 111+/-20 and 118+/-23 mmHg, respectively. Heart rate, renal arterial blood flow and plasma levels of epinephrine and glucose did not change. CONCLUSIONS: Endoluminal NE diminished the increase in pelvic pressure caused by pelvic perfusion even at concentrations too low to cause significant changes in NE plasma levels or systemic effects. Very high NE concentrations in the perfusion fluid caused increased plasma levels and a modest but significant increase in blood pressure. Administration of endoluminal NE may be useful in upper urinary tract stone treatment and endoscopy.     

Vasopressin: another pregnancy protein in human seminal plasma

Human vasopressin (arginine-vasopressin, AVP, antidiuretic hormone, ADH) was estimated, after protein precipitation and extraction in ethanol, using a new radioimmunoassay from Immuno Technology Service, Wijchen, Netherlands. Concentrations in human seminal plasma were 1.84 +/- 1.23 (0.6-4.1) pg/ml, estimated in good duplicates in all 20 samples, where 1 pg = 0.410 uIU/ml WHO 1st 77/501. This is about the same concentration as in blood serum, for which levels up to 8 pg/ml are found by the same kit. In contrast, only trace amounts of vasopressin were found in amniotic fluid at 16-22 weeks of gestation, with zero values in 8 of 19 samples, while another 9 samples showed zero in one duplicate and up to 0.46 pg/ml in the other duplicate, and one sample showed 0.09 pg/ml in good duplicates.     

Influence of vasopressin level on osmotic pressure and sodium concentration in plasma and cerebrospinal fluid in patients with intracranial lesions

To study the influence of the vasopressin level on osmotic pressure and sodium concentration in plasma and cerebrospinal fluid (CSF), plasma and CSF were sampled simultaneously in 27 patients with central nervous system lesions. A significant elevation of arginine vasopressin (AVP) levels in plasma and CSF and a significant increase in the osmotic pressure gradients of plasma and CSF were observed in hyponatremic patients. The significant increases in the osmotic pressure gradients may be attributable to hemodilution and CSF concentration resulting from the elevated AVP level, because the sodium concentration gradients of plasma and CSF did not significantly increase. The elevated AVP levels in plasma and CSF and the increased osmotic pressure gradients of plasma and CSF normalized in parallel with improvement of consciousness. These findings suggest that the increased osmotic pressure gradients of plasma and CSF, derived from increased AVP secretion into blood and CSF, exacerbates brain edema induced by the primary lesion and may contribute to the clinical deterioration of some patients with intracranial lesions.     

Resuscitation with pressors after traumatic brain injury

BACKGROUND: The purpose of the study was to compare initial resuscitation with arginine vasopressin (AVP), phenylephrine (PE), or isotonic crystalloid fluid alone after traumatic brain injury and vasodilatory shock. STUDY DESIGN: Anesthetized, ventilated swine (n = 39, 30 +/- 2 kg) underwent fluid percussion traumatic brain injury followed by hemorrhage (30 +/- 2mL/kg) to a mean arterial pressure < 30mmHg, then were randomized to 1 of 5 groups to maintain mean arterial pressure > 60mmHg for 30 to 60minutes, then cerebral perfusion pressure > 60mmHg for 60 to 300minutes, either unlimited crystalloid fluid only (n = 9), arginine vasopressin + fluid (n = 9), phenylephrine + fluid (n = 9), arginine vasopressin only (n = 5), or phenylephrine only (n = 5). Heterologous transfusions were administered if hematocrit was < 13, and mannitol was administered if intracranial pressure was > 20 mmHg. Cerebrovascular reactivity was evaluated with serial CO(2) challenges. RESULTS: In all groups, physiologic variables were similar at baseline and at the end of shock. On resuscitation, all achieved mean arterial pressure and cerebral perfusion pressure goals. Brain tissue PO(2)s were similar. With fluid only, more blood and mannitol were required, intracranial pressure and peak inspiratory pressure were higher, and cerebrovascular reactivity was decreased (all p < 0.05 versus pressor + fluid). With either pressor + fluid, cardiac output, heart rate, lactate, and mixed venous O(2) saturation were similar to fluid only, but total fluid requirements and urine output were both reduced (p < 0.05). With either pressor only, intracranial pressure remained low, but mixed venous O(2) saturation, cardiac output, and urine output were decreased (all p < 0.05 versus other groups). CONCLUSIONS: To correct vasodilatory shock after traumatic brain injury, a resuscitation strategy that combined either phenylephrine or arginine vasopressin plus crystalloid was superior to either fluid alone or pressor alone.     

Activation of the coagulation system in the subarachnoid space after subarachnoid haemorrhage: Serial measurement of fibrinopeptide A and bradykinin of cerebrospinal fluid and plasma in patients with subarachnoid haemorrhage

Summary Fibrinopeptide A (FPA) levels as an indicator of thrombin activity in the cerebrospinal fluid (CSF) and plasma of 25 patients with subarachnoid haemorrhage (SAH) were measured serially by radioimmunoassay (RIA). FPA levels in CSF were extremely high on days 0–1 (1253±269 ng/ml, mean ± standard error) but decreased rapidly (11.3±3.9 ng/ml on days 2–4, 10.7±5.9 ng/ml on days 5–7, and 6.3±1.5 ng/ml on days 8–14). In the controls the FPA concentration in CSF was 1.2±0.9 ng/ml (mean ± standard deviation). Plasma FPA levels in patients with SAH showed no statistically significant changes with time.The bradykinin (BK) concentration in CSF and plasma in 27 patients with SAH was measured serially by RIA. The cocentrations in CSF were 122.7±22.7 pg/ml (mean ± standard error) on day 0, 38.6±6.1 pg/ml on day 1,22.7±6.3 pg/ml on day 2, and 17.1±3.0 pg/ml or less thereafter. Plasma BK levels in patients with SAH were higher than those in the control group, but there was no statistically significant change over time.From the measurement of FPA it was apparent that the coagulation system in the subarachnoid space is strongly activated in the early stage of SAH. The formation of BK in CSF after SAH is thought to be due to the contact activation of Hageman factor (intrinsic factor) in the subarachnoid space. Trabeculae as collagen bundles in the subarachnoid space were considered to have a possible role in activating the Hageman factor of the coagulation system in SAH.     

ACE inhibition does not exaggerate the blood pressure decrease in the early phase of spinal anaesthesia

BACKGROUND: This study investigates whether long-term treatment with an angiotensin converting enzyme inhibitor (ACEI) impairs the hemodynamic regulation during the early phase of spinal anaesthesia. METHODS: Forty-two patients undergoing minor surgery were studied. Twenty-one patients were long-term treated (ACEI group), while the other patients served as controls (nonACEI group). All patients received a balanced electrolyte solution (6 ml kg(-1)) 20 min before spinal anaesthesia. RESULTS: Mean arterial blood pressure decreased 19% in both groups within 20 min after spinal anaesthesia. Heart rate did not change in either group. Plasma renin concentration increased from 7.3 +/- 2.1 to 12.8 +/- 4 pg ml(-1) during spinal anaesthesia in nonACEI patients (P < 0.05), whereas an elevated plasma renin level remained unchanged in the nonACEI group. The angiotensin II concentration increased in both groups during spinal anaesthesia (P < 0.05). The vasopressin concentration did not change during spinal anaesthesia in the ACEI group, but increased from 1.2 +/- 0.3 to 2.2 +/- 0.5 pg ml(-1) in patients with ACEI treatment (P < 0.05). The norepinephrine concentration increased transiently 5 min after spinal anaesthesia in both groups, and returned to baseline levels within 15 min. CONCLUSION: Long-term ACEI treatment does not further exaggerate the blood pressure decrease in the early phase of spinal anaesthesia. The increase in vasopressin concentrations in ACEI treated patients seems to be sufficient to compensate for the inhibited renin-angiotensin system. In addition, the transient increase in plasma norepinephrine, which occurs independent of preoperative ACEI treatment, seems to be involved in blood pressure regulation during spinal anaesthesia.     

Effect of nerve growth factor on delayed neuronal death after cerebral ischaemia

Summary We investigated the protective action of nerve growth factor (NGF) on delayed neuronal death, and we also studied the involvement of the 200 kDa neurofilament (NF 200) cytoskeletal proteins.Wistar rats were divided into three groups: Group I, in which transient forebrain ischaemia was produced; Group II, ischaemic group which received intraventricular administration of artificial cerebrospinal fluid (CSF); and Group III, ischaemic group which received intraventricular administration of 2 g of 2.5 S NGF. Forebrain ischaemia in these rats was produced by causing transient bilateral occlusion of the common carotid arteries and lowering the mean blood pressure to 50 mmHg for 8 minutes. On the 1st and 7th day after ischaemia we histologically examined neuronal death in the hippocampal CA1 sector.On the 7th day after ischaemia, mean cell death (degenerative cell number/total cell number) was 87±9% in group I (n=7), 51±36% in group II (n=7), and 14±16% in group III (n=8) (p<0.05 vs. group II).The concentration of NF 200 in the hippocampal homogenate was measured by the Western blotting method on the 1st and 7th day after ischaemia. On the 1st day it was found to be 67±11% of that in the control group in group I (n=6), 73±21% in group II (n=6), and 84±7% in group III (n=6) (p<0.05 vs. group II). The concentration of NF 200 in all groups remained at the same level until the 7th day after ischaemia (each group, n=6).These results suggest that 1) intraventricular NGF has a protective effect on delayed neuronal death, 2) these protective actions occur within one day after ischaemia, and 3) these effects may be mediated by the suppressed degradation and/or promoted restoration of neuronal cytoskeletal proteins.     

Effects of epidural anesthesia on catecholamines, renin activity, and vasopressin changes induced by tilt in elderly men

Mean arterial pressure, heart rate, plasma catecholamines, renin activity, and vasopressin changes induced by a 30-degree head-up tilt were studied before and during epidural anesthesia with bupivacaine in eight elderly patients (ages 58-82 yr). The tilt performed before epidural anesthesia did not modify mean arterial pressure, heart rate, plasma catecholamines, renin activity, and vasopressin at 5 and 15 min. During epidural anesthesia, the superior level of analgesia ranged from T4 to T10. Epidural anesthesia induced significant (P less than 0.05) decreases from control values in mean arterial pressure and plasma norepinephrine (from 85 +/- 6 to 67 +/- 8 mmHg and from 600 +/- 108 to 307 +/- 77 pg/ml, respectively, mean +/- SEM) without significant changes in heart rate, plasma epinephrine, renin activity, and vasopressin. However 5 and 15 min after tilt, significant decreases from pretilt values were measured in mean arterial pressure (from 67 +/- 8 to 57 +/- 6 and 55 +/- 6 mmHg, respectively) and in heart rate (from 70 +/- 8 to 63 +/- 7 and 62 +/- 7 beats/min). Simultaneously, an increase in plasma vasopressin (from 14.8 +/- 5.5 to 36.2 +/- 10.3 and 40.0 +/- 10.5 pg/ml) was recorded, whereas plasma norepinephrine and epinephrine remained unchanged. Posttilt plasma renin activity values at 5 and 15 min were increased significantly when compared with the preepidural values (2,752 +/- 1,168, 2,410 +/- 1,214 and 713 +/- 190 pg X ml-1 X h-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of increasing degrees of spinal flexion on cerebrospinal fluid pressure

The effects of increasing degrees of flexion on cerebrospinal fluid pressure were investigated in 12 neurosurgical patients requiring lumbar subarachnoid drains. Cerebrospinal fluid pressure and central venous pressure were measured in three positions: fully flexed ('chin on chest'), flexed at ninety degrees and straight. There was a significant increase in cerebrospinal fluid pressure on moving from the fully flexed to the flexed position (p < 0.0001), but not from the flexed to the straight position. These results were mirrored by smaller changes in central venous pressure. In patients without intracranial pathology these increases in cerebrospinal fluid pressure are probably unimportant. However, intracranial pathology may result in low cerebral perfusion pressures and any increase in cerebrospinal fluid pressure in this group may be harmful. The fully flexed position should be avoided when inserting lumbar drains in at risk patients.     

Increased concentration of atrial natriuretic factor in the cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage and raised intracranial pressure

Plasma and cerebrospinal fluid (CSF) atrial natriuretic factors/peptides (ANFs/ANPs) were measured in 26 patients with normal or raised intracranial pressure (ICP) by means of an instant radioreceptor assay. All 26 patients were suffering from aneurysmal subarachnoid hemorrhage (SAH), and 11 had also developed raised ICP (ICP greater than 20 mm Hg). In SAH patients with normal ICP, the plasma levels of ANF were 20 to 200 pg/ml (mean +/- SE, 89 +/- 68 pg/ml); in the 11 SAH patients with raised ICP, however, ANF levels were 14 to 262 pg/ml (mean 114 +/- 79 pg/ml). The difference was not statistically significant. The ANF/ANP plasma levels in 6 healthy volunteers were 15 to 167 pg/ml (mean 77 +/- 32 pg/ml). Although the ANF/ANP concentration in the CSF of patients with normal ICP did not reach the lower limit of detectability (i.e., 4 pg/ml) in any case, in those with elevated ICP it was 14 to 120 pg/ml (mean 49 +/- 37 pg/ml). This difference was statistically highly significant. The results of this preliminary study suggest that the ANF/ANP concentration in human CSF is 1 to 2 orders lower than that in the plasma and that there is no significant correlation between ANF/ANP levels in the CSF and the plasma. After SAH in patients with raised ICP, there was an accompanying increase in the ANF/ANP concentration in the CSF, but the ANF/ANP concentration in the plasma was not changed significantly. Accordingly, a central ANF/ANP release might be hypothesized to play a causative or adaptive role in the neuroendocrine regulation of ICP dynamics, although this may simply be an epiphenomenon.     

The resistance of a lymph node to lymph flow

The relationship between lymph flow, lymph node arterial and venous perfusion pressure and lymph node resistance have been studied in an in vivo isolated canine iliac lymph node perfused through an afferent lymphatic with heparinized canine plasma. The relationship between the rate of perfusion and perfusion pressure across the node was linear but the calculated resistance of the node decreased as the rate of perfusion increased. In nine dogs the mean resistance to lymph flows less than 0.1 ml/min was 180 mmHg/ml min, but 68 mmHg/ml min to rates of perfusion above 1.0 ml/min. An increase of venous pressure in the veins draining the node increased the node's resistance by 8.6 mmHg/ml min for each 10 mmHg increase of venous pressure. The effect on node resistance of an increase of venous pressure was greater at low rates of perfusion. A decrease of arterial pressure in the arteries supplying the node reduced the node's resistance by 2 mmHg/ml min for each 10 mmHg decrease of arterial pressure. Increases of arterial pressure had an opposite effect of a similar magnitude. The effect on node resistance of a change of arterial pressure in either direction was greater at low rates of perfusion.     

The effects of verapamil on cerebrospinal fluid pressure in surgical patients

The effects of verapamil upon cerebrospinal fluid pressure (CSFP) were studied in twenty surgical patients without intracranial pathology who were divided into two groups of ten patients each: verapamil 0.075mg·kg^–1 was given in group 1 and 0.15mg·kg^–1 was given in group 2. A spinal needle was inserted into the subarachnoid space to permit continuous measurement of CSFP. Intravenous verapamil as a bolus produced a statistically significant increase in CSFP: from 6.0 ± 3.5 (mean ± SD) to 10.5 ± 4.3mmHg in group 1 (P < 0.01), and from 6.2 ± 3.1 to 12.6 ± 3.8mmHg in group 2 (P < 0.01). CSFP after verapamil attained its maximum in 0.5–1.5min, then gradually returned to control levels. Changes in CSFP were always associated with statistically significant decreases in arterial blood pressure and cerebral perfusion pressure, while the heart rate showed variable changes. It is concluded that a clinical dose of verapamil showed variable changes. It is concluded that a clinical dose of verapamil (0.075–0.15mg·kg^–1) has no neurological side effects in patients without intracranial hypertension. However, it must be emphasized that verapamil may increase CSFP to undesirable levels and should be avoided in patients with compromised intracranial compliance.(Nishikawa T, Namiki A: The effects of verapamil on cerebrospinal fluid pressure in surgical patients. J Anesth 1: 132–136, 1987)     

Plasma Vasopressin Levels and Urinary Sodium Excretion during Cardiopulmonary Bypass with and without Pulsatile Flow

The use of pulsatile perfusion during bypass should create a more physiological milieu and thus attenuate the vasopressin stress response. To determine this, 20 patients scheduled for elective coronary artery bypass operation were studied in two groups. Group 1 had standard nonpulsatile perfusion, and in Group 2 a pulsatile pump was used. Measurements were made before and after anesthesia, after surgical incision, and at 15 and 30 minutes during and after cardiopulmonary bypass.In both groups, vasopressin levels were significantly elevated after sternotomy (4.5 ± 1.5 to 37 ± 10 pg/ml in Group 1 and 3.1 ± 1.2 to 33 ± 9 pg/ml in Group 2, p < 0.05) and during bypass (198 ± 19 pg/ml in Group 1 and 113 ± 16 pg/ml in Group 2) but were higher in Group 1 (p < 0.05). With comparable perfusion pressures in both groups, Group 2 required higher flow (4.5 ± 0.2 versus 3.5 ± 0.3 L/min, p < 0.05) and had lower resistance (1,351 ± 182 versus 1,841 ± 229 dynes sec cm^-5, p < 0.05) and higher urine Na⁺ (123 ± 5 versus 101 ± 8 mEq/L, p < 0.05). These data demonstrate that pulsatile flow can significantly attenuate the vasopressin stress response to bypass. Since vasopressin, at these concentrations, is a potent vasoconstrictor and is capable of producing a Na⁺ diuresis, this may partially explain the higher flow requirements and the decrease in Na⁺ excretion.     

Recurrent hypertonic dehydration due to selective defect in the osmoregulation of thirst

A 6-year-old girl with recurrent episodes of hypertonic dehydration was studied. She denied thirst even with a plasma osmolality as high as 421 mosmol/kg. The hypernatremia was associated with an ability to concentrate urine (854 mosmol/kg). Volume expansion with water corrected hypernatremia (162 to 148 mEq/l) and resulted in an increased urine flow and urinary dilution (137 mosmol/kg) because of suppression of endogenousvasopressin (AVP) release (5.1 pg/ml). Hypertonic saline infusion raised the plasma AVP level (25.6 pg/ml) in response to changes in plasma osmolality (305 to 330 mosmol/kg) and led to a maximal urine osmolality of 818 mosmol/kg. With chronic forced fluid intake, the patient maintained a normal resum sodium concentration (range, 135–145 mEq/l) with a urine osmolality as low as 65 mosmol/kg. These findings are consistent with an isolated defect in the osmoregulation of thirst as the cause of the chronic hypertonic dehydration without deficiency in AVP secretion.     

Sympathetic blockade by epidural anesthesia attenuates the cardiovascular response to severe hypoxemia

Blood pressure is usually well maintained during epidural or spinal anesthesia even in the presence of extensive sympathetic blockade. The authors investigated whether hormonal systems support arterial pressure and how the circulation copes with a hypoxic challenge when activation of the sympathetic nervous system is selectively impaired by neural blockade. Accordingly, the effects of high epidural anesthesia alone and combined with hypoxia were evaluated in seven awake trained dogs. On different days, either bupivacaine 0.5% (8-12 ml) or saline (placebo) were randomly injected epidurally and the effects evaluated on cardiovascular (arterial pressure, heart rate) and respiratory (blood gases, oxygen consumption) variables, as well as on hormone plasma concentrations (vasopressin, norepinephrine, epinephrine, renin) during both normoxia and hypoxia. During epidural anesthesia alone, vasopressin increased tenfold (1.7 pg/ml +/- 1.0 SD to 16.8 +/- 13.8, P less than 0.05), norepinephrine decreased (90 pg/ml +/- 31 to 61 +/- 28, P less than 0.05) while epinephrine and renin concentrations remained unchanged. Mean arterial and pulse pressure decreased by 13 mmHg and 23 mmHg (P less than 0.05), respectively. In dogs without sympathetic blockade (saline group), hypoxemia (PaO2: 31 +/- 4 mmHg) evoked an increase in mean blood pressure by 37 mmHg +/- 8 and heart rate by 50 beats per min +/- 17. In contrast, in the presence of sympathetic blockade but with a similar degree of hypoxemia, blood pressure failed to increase (+ 1 mmHg +/- 14) and heart rate rose by only 15 beats per min +/- 11. These differences between groups were statistically significant (P less than 0.001). Hypoxemia induced a similar hypocarbia (PaCO2:25 mmHg) in both groups, indicating that the ventilatory response to hypoxemia was preserved after epidural blockade. During hypoxemia vasopressin concentrations increased 35-fold to 64 pg/ml +/- 38 (P less than 0.0001) compared to base line only during epidural anesthesia, but not after epidural saline (2 pg/ml +/- 2), while other hormones showed no significant differences. The authors conclude that high epidural anesthesia in awake unsedated dogs: 1) almost completely abolishes the normal cardiovascular response to hypoxemia while promoting vasopressin secretion; 2) preserves the ventilatory response to hypoxemia; and 3) is associated with increased vasopressin concentrations, most likely to compensate for decreased cardiac filling and/or arterial blood pressure when sympathoadrenal responses are impaired. Thus, the changes in cardiovascular vital signs in response to severe hypoxemia are markedly blunted when spinal sympathetic outflow is selectively eliminated by epidural anesthesia.     

The influence of the decompressive operation on the intracranial pressure and the pressure-volume relation in patients with severe head injuries

Summary Measurements of intracranial pressure by ventricular catheter were performed in 47 patients with severe head injuries. Thirty-three patients with decompressive operations such as osteoclastic craniotomy and dilatation by means of duraplastic have been compared with 14 patients with closed heads with regard to volume pressure response (intracranial elasticity). This was determined either by intraventricular injection of 2 ml saline or by drainage of cerebrospinal fluid. The examination clearly shows that patients with closed heads have a much higher intracranial elasticity than patients who have decompressive operations, so that in the first group minor differences of the intracranial volume cause extreme deviations of the intracranial pressure. Therefore, the decompressive operation has been advised in severe head injuries with increased intracranial pressure as a measure additional to high dose dexamethasone therapy and hyperventilation.     

Clinical study of ventriculo-lumbar perfusion in the patients of so-called normal pressure hydrocephalus (author's transl)

The cerebrospinal fluid dynamics were studied in the ten patients between 33 and 67 years old with signs of so-called normal pressure hydrocephalus by the technique of ventriculo-lumbar perfusion. The perfusion fluid with Ringer's solution or Hartmann's solution containing tracer amounts (25 mg/dl) of insulin. The inflow fluid warmed up to the body temperature was introduced by the infusion pump to the trigone of the lateral ventricle through the ventricular tube. The outflow fluid was collected from the lumbar subarachnoid space through the spinal needle inserted into the L4-5 interspace. The perfusion pressure was adjusted by raising and lowering the height of the outflow manometric pressure relative to the spinous process. The distribution volume of the perfusion system was the range of 94 - 209 ml (average 136 ml) and exceeded the normal range. The formation rate of cerebrospinal fluid was the range of 0.21 - 0.69 ml/min (average 0.39 ml/min) at the opening pressure, and nearly equal to the bulk absorption rate. There was the relationship between the bulk absorption rate and the perfusion pressure, and the regression coefficients in nine cases were lower than reported in normals. The clinical condition of seven of the nine patients demonstrating this absorptive deficit improved after cerebrospinal fluid shunting. The perfusion test was useful to recognize the cerebrospinal fluid dynamics and also to determine the indication of cerebrospinal fluid shunt in the patients of so-called normal pressure hydrocephalus.     

Renin-angiotensin-aldosterone system and vasopressin in cyclosporine-treated renal allograft recipients

Eleven patients, who had undergone renal transplantation and who had hypertension, aged 19-56 years, were treated with cyclosporine and prednisolone. We measured plasma renin activity, aldosterone and vasopressin (RIAs) at the first, second and third week and again 9 to 12 months after transplantation. Plasma renin activity was in the low-normal range throughout (0.31 +/- 0.05, 0.30 +/- 0.03, 0.32 +/- 0.05 ng/ml/h on short- vs. 0.32 +/- 0.04 ng/ml/h on long-term), aldosterone showed a tendency to decrease (114 +/- 27, 72 +/- 18, 71 +/- 11 pg/ml on short- vs. 54 +/- 23 pg/ml on long-term), whereas vasopressin remained moderately increased during the observation period (10.5 +/- 0.8, 10.4 +/- 1.6, 8.9 +/- 0.6 pg/ml on short- vs. 9.6 +/- 1.0 pg/ml on long-term). We then investigated the reactivity of the renin-system in 5 of the patients by stimulating renin release by captopril. Increases in plasma renin activity were only moderate (0.35 +/- 0.03 vs. 0.66 +/- 0.21 ng/ml/h) and blood pressure dropped only slightly (148 +/- 2.0/98 +/- 1.2 vs. 141 +/- 4.6/95 +/- 4.2 mmHg). Levels of plasma aldosterone were significantly suppressed from a low baseline (46.4 +/- 13.5 vs. 25.3 +/- 6.1 pg/ml, p less than 0.05). The increase in vasopressin was unaffected by captopril (9.6 +/- 1.0 vs. 8.8 +/- 0.4 pg/ml). Our results suggest that in renal transplantation patients with good graft function, the activity of the renin system is unaffected by cyclosporine treatment on short- and on long-term. Vasopressin stimulation does not seem to depend on the renin system and might play a role as a vasoconstrictor in the face of a denervated kidney.