Cerebral autoregulatory performance and the cerebrovascular response to head-of-bed positioning in acute ischaemic stroke.

BACKGROUND AND PURPOSE: Cerebrovascular responses to head-of-bed positioning in patients with acute ischaemic stroke are heterogeneous, questioning the applicability of general recommendations on head positioning. Cerebral autoregulation is impaired to various extents after acute stroke, although it is unknown whether this affects cerebral perfusion during posture change. We aimed to elucidate whether the cerebrovascular response to head position manipulation depends on autoregulatory performance in patients with ischaemic stroke. METHODS: The responses of bilateral transcranial Doppler ultrasound-determined cerebral blood flow velocity (CBFV) and local cerebral blood volume (CBV), assessed by near-infrared spectroscopy of total hemoglobin tissue concentration ([total Hb]), to head-of-bed lowering from 30° to 0° were determined in 39 patients with acute ischaemic stroke and 17 reference subjects from two centers. Cerebrovascular autoregulatory performance was expressed as the phase difference of the arterial pressure-to-CBFV transfer function. RESULTS: Following head-of-bed lowering, CBV increased in the reference subjects only ([total Hb]: + 2.1 ± 2.0 vs. + 0.4 ± 2.6 µM; P < 0.05), whereas CBFV did not change in either group. CBV increased upon head-of-bed lowering in the hemispheres of patients with autoregulatory performance <50th percentile compared with a decrease in the hemispheres of patients with better autoregulatory performance ([total Hb]: +1.0 ± 1.3 vs. -0.5 ± 1.0 µM; P < 0.05). The CBV response was inversely related to autoregulatory performance (r = -0.68; P < 0.001) in the patients, whereas no such relation was observed for CBFV. CONCLUSION: This study is the first to provide evidence that cerebral autoregulatory performance in patients with acute ischaemic stroke affects the cerebrovascular response to changes in the position of the head.

Sevoflurane based anaesthesia does not affect already impaired cerebral autoregulation in patients with type 2 diabetes mellitus.

BACKGROUND: The baroreflex regulates arterial blood pressure (BP). During periods when blood pressure changes, cerebral blood flow (CBF) is kept constant by cerebral autoregulation (CA). In patients with diabetes mellitus (DM), low baroreflex sensitivity (BRS) is associated with impaired CA. As sevoflurane-based anaesthesia obliterates BRS, we hypothesised that this could aggravate the already impaired CA in patients with DM resulting in a 'double-hit' on cerebral perfusion leading to increased fluctuations in blood pressure and cerebral perfusion. METHODS: On the day before surgery, we measured CBF velocity (CBFV), heart rate, and BP to determine BRS and CA efficacy (CBFVmean-to-BPmean-phase lead) in 25 patients with DM and in 14 controls. During the operation, BRS and CA efficacy were determined during sevoflurane-based anaesthesia. Patients with DM were divided into a group with high BRS (DMBRS↑) and a group with low BRS (DMBRS↓). Values presented are median (inter-quartile range). RESULTS: Preoperative vs intraoperative BRS was 6.2 (4.5-8.5) vs 1.9 (1.1-2.5, P<0.001) ms mm Hg-1 for controls, 5.8 (4.9-7.6) vs 2.7 (1.5-3.9, P<0.001) ms mm Hg-1 for patients with DMBRS↑, and 1.9 (1.5-2.8) vs 1.1 (0.6-2.5, P=0.31) ms mm Hg-1 for patients with DMBRS↓. Preoperative vs intraoperative CA efficacy was 43° (38-46) vs 43° (38-51, P=0.30), 44° (36-49) vs 41° (32-49, P=0.52), and 34° (28-40) vs 30° (27-38, P=0.64) for controls, DMBRS↑, and DMBRS↓ patients, respectively. CONCLUSIONS: In diabetic patients with low preoperative BRS, preoperative CA efficacy was also impaired. In controls and diabetic patients, CA was unaffected by sevoflurane-based anaesthesia. We therefore conclude that sevoflurane-based anaesthesia does not contribute to a 'double-hit' phenomenon on cerebral perfusion. CLINICAL TRIAL REGISTRATION: NCT 03071432.

The effect of haemodynamic and peripheral vascular variability on cardiac output monitoring: thermodilution and non-invasive pulse contour cardiac output during cardiothoracic surgery.

While haemodynamic variability interferes with the assumption of constant flow underlying thermodilution cardiac output calculation, variability in (peripheral) arterial vascular physiology may affect pulse contour cardiac output methods. We compared non-invasive finger arterial pressure-derived continuous cardiac output measurements (Nexfin® ) with cardiac output measured using thermodilution during cardiothoracic surgery and determined the impact of cardiovascular variability on either method. We compared cardiac output derived from non-invasive finger arterial pressure with cardiac output measured by thermodilution at four grades (A-D) of cardiovascular variability. We defined Grade A data as heart rate and mean arterial pressure variability < 5% and the absence of arrhythmias (implying stable flow) and Physiocal® interval (as measure of variability in finger arterial physiology) > 30 beats. Grade B included all levels of heart rate/mean arterial pressure variability and arrhythmias (Physiocal < 30 excluded). Grade C included all Physiocal intervals (heart rate/mean arterial pressure variability > 5% and arrhythmias excluded). Grade D included all data. Comparison results were quantified as percentage errors. We analysed measurements in 27 patients undergoing coronary artery bypass surgery. Before extracorporeal circulation, the percentage error was 23% (n = 14 patients) in grade A, 28% (n = 20) in grade B, 32% (n = 22) in grade C and 37% (n = 26) in grade D, with a significant increase in variance (p = 0.035). Bias did not differ between grades. After extracorporeal circulation (n = 27), percentage errors became larger, but were not different between grades. Variability during cardiothoracic surgery affected the comparison between thermodilution and non-invasive finger arterial pressure-derived cardiac output. When the main sources of variability were included, percentage errors were large. Future cardiac output methodology comparison studies should report haemodynamic variability.

Novel method for intraoperative assessment of cerebral autoregulation by paced breathing.

Background: Cerebral autoregulation (CA) is the mechanism that maintains constancy of cerebral blood flow (CBF) despite variations in blood pressure (BP). Patients with attenuated CA have been shown to have an increased incidence of peri-operative stroke. Studies of CA in anaesthetized subjects are rare, because a simple and non-invasive method to quantify the integrity of CA is not available. In this study, we set out to improve non-invasive quantification of CA during surgery. For this purpose, we introduce a novel method to amplify spontaneous BP fluctuations during surgery by imposing mechanical positive pressure ventilation at three different frequencies and quantify CA from the resulting BP oscillations. Methods: Fourteen patients undergoing sevoflurane anaesthesia were included in the study. Continuous non-invasive BP and transcranial Doppler-derived CBF velocity (CBF V ) were obtained before surgery during 3 min of paced breathing at 6, 10, and 15 bpm and during surgery from mechanical positive pressure ventilation at identical frequencies. Data were analysed using frequency domain analysis to obtain CBF V -to-BP phase lead as a continuous measure of CA efficacy. Group averages were calculated. Values are means ( sd ), and P <0.05 was used to indicate statistical significance. Results: Preoperative vs intraoperative CBF V -to-BP phase lead was 43 (9) vs 45 (8)°, 25 (8) vs 24 (10)°, and 4 (6) vs -2 (12)° during 6, 10, and 15 bpm, respectively (all P =NS). Conclusions: During surgery, cerebral autoregulation indices were similar to values determined before surgery. This indicates that CA can be quantified reliably and non-invasively using this novel method and confirms earlier evidence that CA is unaffected by sevoflurane anaesthesia. Clinical trial registration: NCT03071432.

Middle cerebral artery blood velocity during running.

Running induces characteristic fluctuations in blood pressure (BP) of unknown consequence for organ blood flow. We hypothesized that running-induced BP oscillations are transferred to the cerebral vasculature. In 15 healthy volunteers, transcranial Doppler-determined middle cerebral artery (MCA) blood flow velocity, photoplethysmographic finger BP, and step frequency were measured continuously during three consecutive 5-min intervals of treadmill running at increasing running intensities. Data were analysed in the time and frequency domains. BP data for seven subjects and MCA velocity data for eight subjects, respectively, were excluded from analysis because of insufficient signal quality. Running increased mean arterial pressure and mean MCA velocity and induced rhythmic oscillations in BP and in MCA velocity corresponding to the difference between step rate and heart rate (HR) frequencies. During running, rhythmic oscillations in arterial BP induced by interference between HR and step frequency impact on cerebral blood velocity. For the exercise as a whole, average MCA velocity becomes elevated. These results suggest that running not only induces an increase in regional cerebral blood flow but also challenges cerebral autoregulation.

Orthostatic leg blood volume changes assessed by near-infrared spectroscopy.

Standing up shifts blood to dependent parts of the body, and blood vessels in the leg become filled. The orthostatic blood volume accumulation in the small vessels is relatively unknown, although these may contribute significantly. We hypothesized that in healthy humans exposed to the upright posture, volume accumulation in small blood vessels contributes significantly to the total fluid volume accumulated in the legs. Considering that near-infrared spectroscopy (NIRS) tracks postural blood volume changes within the small blood vessels of the lower leg, we evaluated the NIRS-determined changes in oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total haemoglobin tissue concentration (Δ[tHb]) and in total leg volume by strain-gauge plethysmography during 70 deg head-up tilt (HUT; n = 7). In a second experiment, spatial and temporal reproducibility were evaluated with three NIRS probes applied on two separate days (n = 8). In response to HUT, an initially fast increase in [O(2)Hb] was followed by a gradual decline, while [HHb] increased continuously. The increase in [tHb] during HUT was closely related to the increase in total leg volume (r(2) = 0.95 ± 0.03). After tilt back, [O(2)Hb] declined below and [HHb] remained above baseline, whereas all NIRS signals gradually returned to baseline. Spatial heterogeneity was observed, and for two probes [tHb] was highly correlated between days (r(2) = 0.92 ± 0.09 and 0.91 ± 0.12), but less for the third probe (r(2) = 0.44 ± 0.36). The results suggest a non-linear accumulation of blood volume in the small vessels of the leg, with an initial fast phase followed by a more gradual increase at least partly contributing to the relocation of fluid during orthostatic stress.

Pulse contour cardiac output derived from non-invasive arterial pressure in cardiovascular disease.

Pulse contour methods determine cardiac output semi-invasively using standard arterial access. This study assessed whether cardiac output can be determined non-invasively by replacing the intra-arterial pressure input with a non-invasive finger arterial pressure input in two methods, Nexfin CO-trek and Modelflow , in 25 awake patients after coronary artery bypass surgery. Pulmonary artery thermodilution cardiac output served as a reference. In the supine position, the mean (SD) differences between thermodilution cardiac output and Nexfin CO-trek were 0.22 (0.77) and 0.44 (0.81) l.min(-1) , for intra-arterial and non-invasive pressures, respectively. For Modelflow, these differences were 0.70 (1.08) and 1.80 (1.59) l.min(-1) , respectively. Similarly, in the sitting position, differences between thermodilution cardiac output and Nexfin CO-trek were 0.16 (0.78) and 0.34 (0.83), for intra-arterial and non-invasive arterial pressure, respectively. For Modelflow, these differences were 0.58 (1.11) and 1.52 (1.54) l.min(-1) , respectively. Thus, Nexfin CO-trek readings were not different from thermodilution cardiac output, for both invasive and non-invasive inputs. However, Modelflow readings differed greatly from thermodilution when using non-invasive arterial pressure input.

Middle cerebral artery diameter changes during rhythmic handgrip exercise in humans.

Transcranial Doppler (TCD) sonography is a frequently employed technique for quantifying cerebral blood flow by assuming a constant arterial diameter. Given that exercise increases arterial pressure by sympathetic activation, we hypothesized that exercise might induce a change in the diameter of large cerebral arteries. Middle cerebral artery (MCA) cross-sectional area was assessed in response to handgrip exercise by direct magnetic resonance imaging (MRI) observations. Twenty healthy subjects (11 female) performed three 5 min bouts of rhythmic handgrip exercise at 60% maximum voluntary contraction, alternated with 5 min of rest. High-resolution 7 T MRI scans were acquired perpendicular to the MCA. Two blinded observers manually determined the MCA cross-sectional area. Sufficient image quality was obtained in 101 MCA-scans of 19 subjects (age-range 20-59 years). Mixed effects modelling showed that the MCA cross-sectional area decreased by 2.1 ± 0.8% (p = 0.01) during handgrip, while the heart rate increased by 11 ± 2% (p < 0.001) at constant end-tidal CO2 (p = 0.10). In conclusion, the present study showed a 2% decrease in MCA cross-sectional area during rhythmic handgrip exercise. This further strengthens the current concept of sympathetic control of large cerebral arteries, showing in vivo vasoconstriction during exercise-induced sympathetic activation. Moreover, care must be taken when interpreting TCD exercise studies as diameter constancy cannot be assumed.

Orthostatic blood pressure control before and after spaceflight, determined by time-domain baroreflex method.

Reduction in plasma volume is a major contributor to orthostatic tachycardia and hypotension after spaceflight. We set out to determine time- and frequency-domain baroreflex (BRS) function during preflight baseline and venous occlusion and postflight orthostatic stress, testing the hypothesis that a reduction in central blood volume could mimic the postflight orthostatic response. In five cosmonauts, we measured finger arterial pressure noninvasively in supine and upright positions. Preflight measurements were repeated using venous occlusion thigh cuffs to impede venous return and "trap" an increased blood volume in the lower extremities; postflight sessions were between 1 and 3 days after return from 10- to 11-day spaceflight. BRS was determined by spectral analysis and by PRVXBRS, a time-domain BRS computation method. Although all completed the stand tests, two of five cosmonauts had drastically reduced pulse pressures and an increase in heart rate of approximately 30 beats/min or more during standing after spaceflight. Averaged for all five subjects in standing position, high-frequency interbeat interval spectral power or transfer gain did not decrease postflight. Low-frequency gain decreased from 8.1 (SD 4.0) preflight baseline to 6.8 (SD 3.4) postflight (P = 0.033); preflight with thigh cuffs inflated, low-frequency gain was 9.4 (SD 4.3) ms/mmHg. There was a shift in time-domain-determined pulse interval-to-pressure lag, Tau, toward higher values (P < 0.001). None of the postflight results were mimicked during preflight venous occlusion. In conclusion, two of five cosmonauts showed abnormal orthostatic response 1 and 2 days after spaceflight. Overall, there were indications of increased sympathetic response to standing, even though we can expect (partial) restoration of plasma volume to have taken place. Preflight venous occlusion did not mimic the postflight orthostatic response.

Muscle tensing during standing: effects on cerebral tissue oxygenation and cerebral artery blood velocity.

BACKGROUND AND PURPOSE: When standing up causes dizziness, tensing of the leg muscles may alleviate the symptoms. We tested the hypothesis that leg tensing improves orthostatic tolerance via enhanced cerebral perfusion and oxygenation. METHODS: In 10 healthy young adults, the effects of leg tensing on transcranial Doppler-determined middle cerebral artery (MCA) mean blood velocity (V(mean)) and the near-infrared spectroscopy-determined frontal oxygenation (O(2)Hb) were assessed together with central circulatory variables and an arterial pressure low-frequency (LF) (0.07 to 0.15 Hz) domain evaluation of sympathetic activity. RESULTS: Standing up reduced central venous pressure by (mean+/-SEM) 4.3+/-2.6 mm Hg, stroke volume by 49+/-7 mL, cardiac output by 1.9+/-0.4 L/min, and mean arterial pressure at MCA level by 9+/-4 mm Hg, whereas it increased heart rate by 30+/-4 beats per minute (P<0.05). MCA V(mean) declined from 67+/-4 to 56+/-3 cm/s, O(2)Hb decreased by 7+/-2.8%, and LF spectral power increased (P<0.05). Leg tensing increased central venous pressure by 1.4+/-2.7 mm Hg and cardiac output by 1.8+/-0.4 L/min with no significant effect on blood pressure, whereas heart rate decreased by 11+/-3 beats per minute (P<0.05). MCA V(mean) increased to 63+/-3 cm/s and O(2)Hb increased by 2.1+/-2.6%, whereas LF power declined (P<0.05). Within 2 minutes after leg tensing, these effects had disappeared. CONCLUSIONS: During standing, tensing of the leg muscles attenuates a reduction in cerebral perfusion and oxygenation as it stabilizes central circulatory variables and reduces sympathetic activity.

Middle cerebral artery blood velocity during a valsalva maneuver in the standing position.

Occasionally, lifting of a heavy weight leads to dizziness and even to fainting, suggesting that, especially in the standing position, expiratory straining compromises cerebral perfusion. In 10 subjects, the middle cerebral artery mean blood velocity (V(mean)) was evaluated during a Valsalva maneuver (mouth pressure 40 mmHg for 15 s) both in the supine and in the standing position. During standing, cardiac output decreased by 16 +/- 4 (SE) % (P < 0.05), and at the level of the brain mean arterial pressure (MAP) decreased from 89 +/- 2 to 78 +/- 3 mmHg (P < 0.05), as did V(mean) from 73 +/- 4 to 62 +/- 5 cm/s (P < 0.05). In both postures, the Valsalva maneuver increased central venous pressure by approximately 40 mmHg with a nadir in MAP and cardiac output that was most pronounced during standing (MAP: 65 +/- 6 vs. 87 +/- 3 mmHg; cardiac output: 37 +/- 3 vs. 57 +/- 4% of the resting value; P < 0.05). Also, V(mean) was lowest during the standing Valsalva maneuver (39 +/- 5 vs. 47 +/- 4 cm/s; P < 0.05). In healthy individuals, orthostasis induces an approximately 15% reduction in middle cerebral artery V(mean) that is exaggerated by a Valsalva maneuver performed with 40-mmHg mouth pressure to approximately 50% of supine rest.

Assessment of cardiovascular reflexes: influence of posture and period of preceding rest.

The aim of the present study was to investigate the effects of a pretest redistribution of blood volume and of a change in the neurohumoral condition on the blood pressure (BP) and heart rate (HR) responses to three commonly used cardiovascular reflex tests: standing up, forced breathing, and the Valsalva maneuver in 10 healthy male subjects. Base-line conditions were altered by changing posture and the duration of rest preceding the test stimulus. A continuous recording of finger BP was obtained noninvasively by a Finapres. The main observations from this study are with respect to standing up: lengthening the period of preceding rest from 1 to 20 min enlarges the initial BP (systolic/diastolic) decrease (from 8 +/- 10/9 +/- 4 to 27 +/- 8/19 +/- 4 mmHg, P less than 0.01) and the subsequent BP overshoot (from 17 +/- 10/12 +/- 7 to 31 +/- 10/18 +/- 7 mmHg, P less than 0.05); to forced breathing: inspiratory-expiratory changes in BP but not in HR are larger in the upright posture (P less than 0.05); and to the Valsalva maneuver: change in posture from supine to standing increases the phase II BP decrease (from 18 +/- 12/8 +/- 6 to 45 +/- 16/21 +/- 9 mmHg), phase IV systolic BP overshoot (from 26 +/- 16 to 71 +/- 17 mmHg), delta HRmax (from 30 +/- 10 to 47 +/- 12 beats/min), and the Valsalva ratio (HRmax/HRmin), from 2.0 +/- 0.3 to 2.6 +/- 0.7, all significant at P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrasting effects of acute and chronic volume expansion on orthostatic blood pressure control in a patient with autonomic circulatory failure.

We studied the effects of acute and chronic volume expansion on orthostatic blood pressure control in a 22-year-old female with hypoadrenergic orthostatic hypotension. Acute volume expansion on two occasions had unexpected effects: a decrease respectively no change in orthostatic tolerance and no change in upright blood pressure immediately after volume expansion followed by a marked improvement 8 h thereafter. The time course of changes in haematocrit and serum protein indicated an initial extravasation of plasma followed by a subsequent larger fluid shift back to the intravascular space. These effects had vanished after 3 days. Chronic volume expansion by head-up tilt at night and fludrocortisone resulted in a marked improvement in orthostatic blood pressure control at a comparable increment in body weight and sodium balance for the next 7 years until now. The circadian circulatory variation with orthostatic blood pressure lowest in the morning remained present after chronic volume expansion. We conclude in this patient that the effects of acute volume expansion on orthostatic blood pressure in autonomic failure are complex and not predictive for the beneficial effects of chronic volume expansion.

Singing-induced hypotension: a complication of a high spinal cord lesion.

Cardiovascular autonomic control was studied in a patient with an incomplete high spinal cord lesion who presented with the symptoms of severe dizziness during debating and singing but not during orthostasis. The marked falls in blood pressure upon singing and orthostasis (45 degrees passive head-up tilt) were comparable in magnitude but different in time course. The fall in blood pressure upon graded Valsalva manoeuvres, however, was comparable to singing in magnitude and time course; similarly, 20 and 30 mmHg strain evoked complaints of dizziness. These differential circulatory responses upon orthostasis versus singing and Valsalva in tetraplegic patients have not been described before. We suggest that rapidly developing hypotension such as that induced by a moderate Valsalva strain represents the instantaneous mechanical effects of a raised intrathoracic pressure with lack of abdominal compression on the cardiovascular system when baroreflex vasomotor modulation is disrupted.

Orthostatic hypotension caused by sympathectomies performed for hyperhidrosis.

We studied sympathetic cardiovascular control in a patient after sympathectomies and found severe hypoadrenergic orthostatic hypotension before and after, but not during upright exercise. This report is the first to correlate in man anatomical sympathetic lesions with autonomic function test results and to document that in a sequence of sympathectomies orthostatic hypotension does not develop until the major part of splanchnic sympathetic outflow is destroyed.

Bilateral kidney rupture with severe retroperitoneal bleeding in polyarteritis nodosa.

A patient is described with nontraumatic subcapsular haematomas of both kidneys, complicated by severe retroperitoneal bleeding. A diagnosis of polyarteritis nodosa was reached using renal angiography. Bilateral nephrectomy had to be performed because of uncontrollable renal bleeding. A review of the literature on this complication of polyarteritis nodosa is given.

Hemodynamic effects of intermittent manual lung hyperinflation in patients with septic shock.

OBJECTIVE: The purposes of this study were to investigate the hemodynamic changes induced by intermittent manual lung hyperinflation (MHI) and to assess if these changes are adverse enough to warrant prohibition of MHI as a routine procedure in the care of patients with septic shock. DESIGN: The study's design was experimental prospective. SETTING: The settings were university hospital intensive care units. PATIENTS: Subjects included 13 consecutive mechanically ventilated patients with septic shock who met the inclusion criteria. MEASUREMENTS AND RESULTS: Phasic MHI-related increments in mean inspiratory airway pressure were concordant to changes in mean pulmonary artery pressure (MPAP) (r(2) = 0.67) with a 0.6 mm Hg rise in MPAP per cm H(2)O airway pressure. The magnitude of MPAP changes was not reflected in magnitude of stroke volume index (SVI) (r(2) = 0.06). On average, MHI did not induce statistically significant hemodynamic changes and mean values returned to baseline level within 15 minutes. SVI during MHI increased slightly in 9 patients, from 37 +/- 15 (mean +/- SD) to 41 +/- 17 mL/m(2) (P <.05), and decreased in 4, from 60 +/- 10 to 50 +/- 14 mL/m(2) (not significant). Patients with an increase in SVI had lower baseline values for SVI, cardiac index, and left ventricular stroke work index (P <.05) and higher values for systemic vascular resistance index compared with patients with a decrease in SVI (P <.05). Left ventricular stroke work index was higher in patients with a decrease in SVI than in patients with an increase in SVI (52 +/- 9 vs 34 +/- 8; P <.05). Tidal volume increased from 499 +/- 176 mL before MHI to 587 +/- 82 mL, 5 minutes after MHI (P <.05) with a return to baseline values within 15 minutes after the procedure. CONCLUSION: The hemodynamic effects of intermittent MHI in patients with septic shock are relatively small and insignificant and seem to be related to the cardiovascular state before the procedure. The risk of inducing hemodynamic changes with MHI should not be considered as a contraindication in patients with septic shock who are mechanically ventilated.

Assessment of cardiovascular reflexes is of limited value in predicting maximal +Gz-tolerance.

The importance of +Gz-induced loss of consciousness as a major cause of inflight incapacitation emphasizes the need for predicting +Gz-tolerance and investigating its possible determinants. The cardiovascular changes from +Gz-stress are initially counteracted reflexly by the cardiovascular autonomic system. The integrity of neural cardiovascular reflex control can be assessed by analysing the blood pressure (BP) and heart rate (HR) responses to different maneuvers, such as the Valsalva maneuver, standing and forced respiratory sinus arrhythmia. The aim of the present study was to investigate a possible relation between the cardiovascular responses to these tests and +Gz-tolerance. In 10 healthy subjects continuous Finapres BP and HR responses to the tests have been determined and correlated with their G-levels of peripheral light loss (PLL) during centrifuge-runs (0.1 G/s). Only mean BP recovery during Valsalva maneuver correlated marginally significantly with PLL (r = 0.63, p = 0.049). Cardiovascular findings were within normal range revealing no cardiovascular autonomic dysfunction. These results indicate that intact neural cardiovascular control seems to be a condition for tolerating +Gz-stress without determining maximal +Gz-tolerance. We conclude that assessment of cardiovascular reflexes may only confirm baroreflex integrity. However, they have limited value in predicting +Gz-tolerance.

[Immunotherapy using the anti-endotoxin antibody HA-1A (Centoxin) in patients with sepsis syndrome; fair results following protocol selection of patients]. / Immunotherapie met de anti-endotoxine-antistof HA-1A (Centoxin) bij patiënten met het sepsissyndroom; matige resultaten na geprotocolleerde selectie van patiënten.

OBJECTIVE: Evaluation of HA-1A treatment in patients with the sepsis syndrome. DESIGN: Descriptive. SETTING: Department of intensive care, Academic Medical Centre, Amsterdam. PATIENTS AND METHODS: Intensive-care patients with the sepsis syndrome and shock or organ failure with a presumptive diagnosis of Gram-negative infection were eligible for treatment with HA-1A. We analysed and compared the results with those of the double-blind, randomized HA-1A study by Ziegler et al. RESULTS: Between May 1991 and March 1992, 27 patients were treated with HA-1A. The mortality rate was 59% (16/27). Among the 11 patients with a Gram-negative bacteraemia mortality was 7/11, much higher than in the Ziegler study (30%). In comparison with the HA-1A study we selected sicker patients: the mean APACHE II score was higher, 93% of our patients were in shock and 85% had organ failure. More patients presented with an intra-abdominal sepsis and mortality in this group was very high (11/14). In patients with a Gram-negative bacteraemia the delay between the onset of the sepsis syndrome and the administration of HA-1A was longer (median 22 h versus 14.3 h in the Ziegler study, mean 30 versus 20 h). CONCLUSION: HA-1A does not appear to be beneficial in critically ill patients with a longstanding sepsis syndrome, especially not if an intra-abdominal sepsis is apparent. Therefore, we decided not to use H-1A until additional data become available. Additional objective inclusion criteria are needed to improve the identification of the patient group that may benefit from treatment with HA-1A.

[Not meningitis but septic shock as the killer in acute meningococcal disease]. / Niet nekkramp, maar septische shock als schrikbeeld acute meningokokkenziekte.

The symptoms and clinical course of meningococcaemia in 14 cases are described; 10 patients died; in one of the four survivors amputations were inevitable for necrosis of hands and feet. The foremost symptoms at the first time that a doctor was contacted were fever, lethargy, petechiae and purpura. The fulminant course is shown by the high number of resuscitation at the time of admission or in the first hours after admission, and by the time between first symptoms and death. The mortality of meningococcaemia is mostly not due to meningitis. Most patients die of septic shock even before signs of meningitis can develop. The early signs of meningococcaemia are not those of meningitis, but those of sepsis. Meningism and headache are rare symptoms. The severest symptoms are fever and lethargy, in combination with petechiae and purpura. The fulminant course of the disease requires immediate admission. Treatment of infection and septic shock may be lifesaving.