The objective of the study was to test the hypothesis that dynamic cerebral pressure-autoregulation is associated with the outcome of patients with severe head injury and to derive optimal criteria for future studies on the predictive value of autoregulation indices. Repeated measurements were performed on 32 patients with severe head injury. Arterial blood pressure (ABP) was measured continuously with an intravascular catheter, intracranial pressure (ICP) was recorded with a subdural semiconductor transducer and cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery. Transfer function analysis was performed on mean beat-to-beat values, using ABP or CBFV as input variables and CBFV or ICP as the output variables. A dynamic index of autoregulation (ARI) ranging between 0 and 9 was extracted from the CBFV step response for a change in ABP. No significant differences between survivors and non-survivors were found due to mean values of ICP, ABP, CPP, CBFV, pCO2, GCS, age or heart rate. The transfer functions between ABP-ICP and CBFV-ICP did not show any significant differences either. The median [lower, upper quartiles] ARI was significantly lower for non-survivors compared with survivors [4.8 (0.0, 5.9) v. 6.9 (5.9, 7.4), p= 0.004]. The correlation between ARI and GOS was also significant (r=0.464, p=0.011). Cohen's coefficient was optimal for a threshold of ARI= 5.86 (kappa 0.51, p=0.0036), leading to a sensitivity for death of 75%, specificity=76.5%, odds ratio =9.75 and overall precision = 75.8%. The difference in ARI values between survivors and non-survivors persisted when results were adjusted for GCS (p = 0.028). A similar analysis for the Marshall CT scale did not reach significance (p = 0.072). A logistic regression analysis confirmed that apart from the ARI, no other variables had a significant contribution to predict outcome. In this group of patients, death following severe head injury could not be explained by traditional indices of risk, but was strongly correlated to indices of dynamic cerebral pressure-autoregulation extracted by means of transfer function analysis. Future studies using a prospective design are needed to validate the predictive value of the ARI index, as estimated by transfer function analysis, in relation to death and other unfavourable outcomes.

1. Autonomic neuropathy is a common complication of diabetes mellitus and is a major risk factor for sudden death. 2. A group of 30 patients with insulin-dependent diabetes mellitus and 30 age-, sex- and blood pressure-matched control subjects underwent traditional tests of autonomic function. Resting supine R-R interval and systolic blood pressure variability were assessed using spectral analysis methods. In addition, we assessed the baroreceptor-cardiac reflex from the linear relation of the change in R-R interval to the increasing systolic blood pressure measured non-invasively with the Finapres monitor during phase 4 of the Valsalva manoeuvre and from resting heart rate and systolic blood pressure power spectra. 3. Whereas standard tests of autonomic function revealed no differences between patients with insulin-dependent diabetes mellitus and control subjects, there was a significant reduction in power spectral density of heart rate variability around the high-frequency region (125.2 +/- 112.9 versus 459.3 +/- 189.8 ms2, mean +/- SD). Furthermore, reductions in baroreflex sensitivity calculated from the Valsalva manoeuvre were detected in diabetics compared with controls (3.3 +/- 1.6 versus 9.5 +/- 2.5 ms/mmHg, mean +/- SD, P < 0.00001). There were significant relations between impairment of the baroreflex and duration of diabetes (P < 0.001) and poor diabetic control (P < 0.05). 4. In summary, autonomic dysfunction occurs much more frequently in diabetic patients than conventional tests would suggest. Abnormal baroreceptor-cardiac reflex sensitivity in patients with insulin-dependent diabetes mellitus may in part be explained by abnormal parasympathetic function. This unrecognized abnormality may have a role in the increased incidence of sudden death seen in young diabetic subjects.

No abstract

We have developed a method to estimate the critical closing pressure (CrCP) of the cerebral circulation based on the intrinsic variability of arterial blood pressure (BP) around stable values of mean arterial pressure (MAP). A consecutive cohort of 33 premature newborns was studied at 6, 12, 24, 48 and 72 hours of age. Cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery and BP was recorded in the abdominal aorta or in a peripheral artery. Continuous measurements lasting five minutes were recorded on digital magnetic tape and signals were digitized at a rate of 200 samples/seconds for processing on a digital computer. Mean values of BP (mBP) and CBFV (mBV) were computed for each cardiac cycle and CrCP was determined as the pressure axis intercept of the regression line of mBV as a function of mBP using 100 sequential heart beats. The resistance-area product (RAP) was obtained from the slope of the regression line. For 57 records (30 patients) the mean +/- SD values of CrCP and RAP were 23.9 +/- 11.6 mmHg and 4.07 +/- 1.83 x 10(4) kg.m-2.s-1, respectively. CrCP has a highly significant correlation with mean arterial pressure (p < 0.001) but RAP has not. Neither CrCP nor RAP are significantly correlated (p > 0.05) with PO2, PCO2, pH, haematocrit, gestational age, birthweight, postnatal age, heart rate on Pourcelot's resistance index. Our results suggest that cerebral perfusion pressure should be defined as MAP-CrCP for normal values of intracranial pressure.

No abstract

The impulse response function (IRF) can express the dynamic relationship between systolic arterial pressure (SAP) and pulse interval (PI) and, consequently, represents an alternative method to assess baroreceptor sensitivity (BRS) in humans. Five normotensive and 13 hypertensive subjects (age 68 +/- 5 yr, range 60-74 yr) were studied at rest in the supine position during baseline conditions and after injections of phenylephrine and sodium nitroprusside. SAP and PI signals were derived from multiple 5-min noninvasive recordings of arterial blood pressure (Finapres) and electrocardiogram. Standard estimates of BRS were obtained by the slopes of transient changes in SAP and PI after the injection of phenylephrine and sodium nitroprusside (BRS(PE) and BRS(SNP)) and by spectral analysis (alpha-index). Impulse responses were obtained by the inverse Fourier transform of the transfer function between PI and SAP. The temporal pattern of the IRF was characterized by a main peak at t = 0, preceded by a "trough" at t = -1 s. A mathematical model of the baroreflex suggests that the peak value of IRF is linearly related to the BRS. The peak value and its smoothed version were shown to be significantly correlated to alpha, BRS(PE), and BRS(SNP) and significantly reduced in the hypertensive group during the three stages of the protocol. We suggest that IRF might be the ideal method to assess BRS because it does not require any subjective preselection of data segments or spectral bands.

Normal pregnancy is associated with marked changes in cardiovascular haemodynamics, which in part may be due to changes in autonomic control mechanisms. Baroreflex sensitivity for heart rate (BRS) was calculated in the supine and standing positions using power spectral analysis of pulse interval (PI) and systolic blood pressure (SBP) in 16 normotensive pregnant women and 10 normotensive non-pregnant controls. The pregnant women were studied on three occasions during their pregnancy (early, mid- and late gestation) and once during the puerperium. Supine total SBP variability increased between early and late pregnancy by 79% [95% confidence intervals (CI) 30%, 145%; P<0. 001], and supine high-frequency PI variability decreased by 75% (CI 51%, 88%; P<0.001). Supine BRS fell by 50% (P<0.001), with values returning to early-pregnancy levels in the puerperium, which were similar to those recorded in the control group. Standing SBP variability and BRS values were unchanged during pregnancy and post partum. The low/high frequency ratio of PI variability, taken as a surrogate measure of sympathovagal balance, increased by 137% (CI 42%, 296%; P<0.01) in the supine but not the standing position from early to late pregnancy. This was due to a decrease in high-frequency variability rather than to an increase in low-frequency variability, suggesting that these changes may have been due to vagal withdrawal rather than increased sympathetic activity. Normotensive pregnancy is associated with a marked decrease in supine BRS, although the exact mechanisms for these changes remain unclear. Further studies are required to define whether changes in BRS and sympathovagal tone in early pregnancy can be used to predict the onset of pregnancy-induced hypertension.

Objective: to examine the relationship between age, blood pressure and cardiac baroreceptor sensitivity derived from spectral analysis, the Valsalva manoeuvre and impulse response function. Methods: we studied 70 healthy normotensive volunteers who were free from disease and not taking medication with cardiovascular or autonomic effects. We measured beat-to-beat arterial blood pressure and used standard surface electrocardiography to record pulse interval under standardized conditions with subjects resting supine as well as during three Valsalva manoeuvres. We performed single, multiple and stepwise regression of patient characteristics against cardiac baroreceptor sensitivity results. Results: there is a non-linear decline in cardiac baroreceptor sensitivity with advancing age, increasing systolic blood pressure and heart rate values (except for the Valsalva-derived result), but little further decline after the fourth decade. Only age significantly influenced values derived using the Valsalva manoeuvre and impulse response analysis. Using spectral analysis, age, systolic and diastolic blood pressure and heart rate influenced cardiac baroreceptor sensitivity, age contributing to 50% of the variability. Age also influenced the relationship between pulse interval and blood pressure, possibly indicating more non-baroreceptor-mediated changes with advancing age. Conclusions: although age is the dominant factor influencing cardiac baroreceptor sensitivity in this normotensive population, there is little change in mean values after 40 years of age. The differences in the relationship between pulse interval and blood pressure with advancing age have implications for the calculation of cardiac baroreceptor sensitivity using spectral analysis.