Gitte Strauss

Hyperventilation restores cerebral blood flow autoregulation in patients with acute liver failure

BACKGROUND/AIMS In patients with acute liver failure loss of cerebral blood flow autoregulation may result from cerebral vasodilatation. Since arterial hypocapnia induces cerebral vasoconstriction, we investigated whether cerebral blood flow autoregulation could be reestablished by mechanical hyperventilation. METHODS Seven consecutive patients (median age 45, range 30-50 years) with acute liver failure and hepatic encephalopathy stage IV entered the study. They were all maintained on mechanical ventilation. Cerebral blood flow autoregulation was evaluated by using transcranial Doppler sonography to assess mean flow velocity (Vmean) in the middle cerebral artery, during a rise in mean arterial pressure by norepinephrine infusion (0.5-10 microg/h). The patients were subsequently hyperventilated for 15 min before cerebral blood flow autoregulation was re-evaluated in the same mean arterial pressure range. RESULTS At baseline PaCO2 (4.0 (3.5-4.9)kPa), all patients had impaired cerebral blood flow autoregulation as Vmean increased from 47 (30-78) to 68 (49-107) cm x s(-1) (p<0.05), as MAP was raised from 82 (60-88) to 106 (89-123) mmHg. During hyperventilation, five of seven patients restored cerebral autoregulation as Vmean remained unchanged at 51 (45-70) cm x s(-1) during a rise in MAP from 84 (65-94) to 110 (89-130) mmHg. Cerebral blood flow autoregulation was not restored in two patients, but hyperventilation reduced the slope of the mean arterial pressure-Vmean correlation. These two patients had renal failure and were treated with intermittent hemodialysis. CONCLUSIONS Cerebral blood flow autoregulation was restored by hyperventilation in five of seven patients with acute liver failure, indicating that cerebral vasodilatation is of pathophysiological importance in dysregulation of cerebral circulation in acute liver failure.

Cerebral Blood Flow and Oxidative Metabolism During Human Endotoxemia

The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), has been suggested to mediate septic encephalopathy through an effect on cerebral blood flow (CBF) and metabolism. The effect of an intravenous bolus of endotoxin on global CBF, metabolism, and net flux of cytokines and catecholamines was investigated in eight healthy young volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique at baseline (during normocapnia and voluntary hyperventilation for calculation of subject-specific cerebrovascular CO2 reactivity), and 90 minutes after an intravenous bolus of a reference Escherichia coli endotoxin. Arterial TNF-α peaked at 90 minutes, coinciding with a peak in subjective symptoms. At this time, CBF and Paco2 were significantly reduced compared to baseline; the CBF decrease was readily explained by hypocapnia. The cerebral metabolic rate of oxygen remained unchanged, and the net cerebral flux of TNF-α, interleukin (IL)-1β, and IL-6 did not differ significantly from zero. Thus, high circulating levels of TNF-α during human endotoxemia do not induce a direct reduction in cerebral oxidative metabolism.

Prevalence of toe nail onychomycosis in diabetic patients.

Onychomycosis among diabetic patients has been reported in some studies to be of high prevalence. This study aimed to investigate the prevalence of onychomycosis among diabetic patients at a Danish University Hospital. Clinical and mycological examinations were performed on type 1 and 2 diabetic patients from in- and out-patient clinics. A total of 271 patients were enrolled, 72% males, mean age 61.3 years, 26% of the patients had diabetes type 1. The prevalence of toe nail onychomycosis (positive culture and/or microscopy) was 22% (n = 59) of which 55 cases were caused by dermatophytes (93%) and 4 cases by yeasts (7%). A correlation was found between onychomycosis and age (p =0.02) and severity of nail changes (p <0.001), respectively. However, no significant correlation was found to gender, type of diabetes, lower extremity arterial disease, neuropathy, toe amputation or oedema. Onychomycosis occurred with a high prevalence in diabetic patients, especially among older patients and those with severe nail changes.

Cerebral perfusion, cardiac output, and arterial pressure in patients with fulminant hepatic failure.

Objective: To evaluate whether changes in cardiac output influence cerebral perfusion directly. In fulminant hepatic failure, the circulation is characterized by wide variations in cardiac output and cerebral blood flow (CBF). Design: A retrospective, interindividual analysis of CBF and cardiac output (part 1) and a prospective evaluation of cerebral perfusion, cardiac output, and arterial pressure during norepinephrine infusion (part 2). Setting: A four‐bed specialist liver failure unit. Patients and Interventions: Twenty patients with fulminant hepatic failure (median age, 43 yrs; range, 17‐54; 13 women) maintained on mechanical ventilation (PaCO2, 33 torr [4.40 kPa]; range, 26‐36 torr [3.47‐4.80 kPa) after development of hepatic encephalopathy, stages 3 to 4, had mean arterial pressure (MAP) and cardiac output determined by radial and pulmonary artery catheters. Cerebral perfusion was measured by the 133Xenon clearance technique (n = 8) and by transcranial Doppler sonography, which was used to measure mean flow velocity (Vmean). CBF and Vmean in patients with high cardiac output (>9 L/min) were compared with those with normal or low cardiac output. In the second part of the study, cerebral autoregulation was evaluated by concomitant measurement of Vmean, cardiac output, and MAP during norepinephrine infusion in nine patients. Measurements and Main Results: Median cardiac output was 8.5 L/min (range, 3.2‐17.3), CBF was 33 mL/100 g/min (12‐77 g/min), and Vmean was 45 cm/sec (22‐65 cm/sec). In patients with elevated cardiac output, MAP, Vmean, and CBF were similar compared with patients with normal cardiac output. Neither CBF nor Vmean correlated to cardiac output. During norepinephrine infusion, Vmean increased from 49 cm/sec (34‐69 cm/sec) to 63 cm/sec (58‐90 cm/sec; p < .05), as MAP increased from 75 mm Hg (54‐105 mm Hg) to 97 mm Hg (90‐128 mm Hg). On average, cardiac output remained unchanged at 5.7 L/min (range, 3.2‐17.3), as it increased in five patients and decreased in four patients. The change in Vmean was related to MAP (r2 = .76; p < .01) but not to cardiac output (r2 = .01). Conclusion: This study shows that CBF correlates to arterial pressure rather than to cardiac output in patients with fulminant hepatic failure. The presence of pressure‐passive cerebral circulation stresses the importance of strict cardiovascular control in securing continuous and sufficient cerebral oxygenation and in avoiding the development of cerebral hyperemia and cerebral edema.

Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis

Cerebral blood flow autoregulation is lost in patients with severe liver cirrhosis. The cause of this is unknown. We determined whether autonomic dysfunction was related to impaired cerebral autoregulation in patients with cirrhosis.Fourteen patients with liver cirrhosis and 11 healthy volunteers were recruited. Autonomic function was assessed in response to deep breathing, head-up tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by determining the change in mean cerebral blood flow velocity (MCAVm, transcranial Doppler) during an increase in blood pressure induced by norepinephrine infusion (NE). The severity of liver disease was assessed using the Child–Pugh scale (class A, mild; class B, moderate; class C, severe liver dysfunction).NE increased blood pressure similarly in the controls (27 (24–32) mmHg) and patients with the most severe liver cirrhosis (Child–Pugh C, 31 (26–44) mmHg, p=0.405 Mann–Whitney). However, the increase in MCAVm was greater in cirrhosis patients compared to the controls (Child–Pugh C, 26 (24–39) %; controls, 3 (−1.3 to 3) %; respectively, p=0.016, Mann–Whitney). HRV during deep breathing was reduced in the cirrhosis patients (Child–Pugh C, 6.0±2.0 bpm) compared to the controls (21.7±2.2 bpm, p=0.001, Tukey’ test). Systolic blood pressure fell during head-up tilt only in patients with severe cirrhosis.Our results imply that cerebral autoregulation was impaired in the most severe cases of liver cirrhosis, and that those with impaired cerebral autoregulation also had severe parasympathetic and sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction was associated with increasing severity of autonomic dysfunction. Although this association is not necessarily causal, we postulate that the loss of sympathetic innervation to the cerebral resistance vessels may contribute to the impairment of cerebral autoregulation in patients with end-stage liver disease.

Cerebral autoregulation in patients with end-stage liver disease.

Objective The aim of the present study was to determine whether cerebral autoregulation is absent in patients with end‐stage liver disease. Design A prospective physiological study Methods Thirty patients, 15 female (median age 50 years, range 33‐74), with biopsy‐proven cirrhosis (4 Child‐Pugh class B, 26 Child‐Pugh class C), had their cerebral perfusion evaluated using mean flow velocity (Vmean) in the middle cerebral artery as measured by transcranial Doppler sonography. Mean arterial pressure (MAP) was raised by intravenous noradrenaline (5‐30 μg/min). Nine patients had no clinical signs of hepatic encephalopathy (HE), three were in HE stage 1, four in HE stage 2, four in HE stage 3 and ten in HE stage 4, respectively. Results Cerebral autoregulation was impaired in 13 patients, as Vmean increased from 47 (26‐88) to 60 (36‐109) cm/s during a rise in MAP from 61 (47‐99) to 82 (65‐121) mmHg. Vmean remained unchanged (preserved cerebral autoregulation) at 56 (30‐119) cm/s in 17 patients when MAP was raised from 74 (59‐90) to 95 (81‐129) mmHg. Cerebral autoregulation was lost in 8/10 patients with HE stage 4 and only in 2/9 patients without HE (P = 0.023). The duration of HE stage 1‐4 before the autoregulation study was identical for patients with preserved cerebral autoregulation compared to patients with impaired cerebral autoregulation, 5 (2‐30) versus 6 (2‐35) days, respectively. Baseline values of MAP were significantly lower in patients with no cerebral autoregulation compared to patients with preserved cerebral autoregulation, 61 (47‐99) versus 74 (59‐90) mmHg (P= 0.012). All other baseline values in the two groups were similar, including PaCO2, albumin, bilirubin, international normalization ratio, galactose elimination capacity, Child‐Pugh class and age. Conclusion Cerebral autoregulation is preserved in most patients with end‐stage liver disease. In patients with hepatic encephalopathy and low MAP, however, cerebral autoregulation is impaired. Eur J Gastroenterol Hepatol 12:767‐771

Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis

Background: The optimal arterial carbon dioxide tension (PaCO2) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO2 reactivity (CO2R), and cerebral metabolic rates (CMR) of oxygen (O2), glucose (glu), and lactate (lac), in patients with ABM and compare the results to those obtained in healthy volunteers.

Cerebrovascular metabolic autoregulation is impaired during liver transplantation.

BACKGROUND We determined whether the coupling between cerebral blood flow (CBF) and oxygen metabolism (CMRO2) is preserved during liver transplantation. Because of cerebrovascular dilatation, we hypothesized that cerebral metabolic autoregulation is impaired, because CBF becomes uncoupled from CMRO2 during the reperfusion phase of the operation. MATERIALS AND METHODS In a prospective study, 13 patients (8 women, median age 46, range 21-6) with liver failure (10 with end-stage chronic liver disease and 3 with acute liver failure) were enrolled. Catheters were placed in a femoral artery and in the internal jugular vein for calculation of the cerebral arteriovenous oxygen content difference (AVDO2). CBF was recorded by the 133Xenon injection technique, and by transcranial Doppler sonography determined mean flow velocity (Vmean) in the middle cerebral artery. The CMRO2 was calculated as the AVDO2 times CBF and the cerebrovascular resistance (CVR) as the mean arterial pressure to CBF ratio. An index of large cerebral artery diameter was expressed by the CBF to Vmean ratio. RESULTS From induction of anesthesia to the anhepatic period, CBF decreased from a median of 47 (interquartiles 31-55) to 41 (37-48) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged (1.3 [0.9-2.5] vs. 1.7 [0.9-2.3] ml 100 g(-1) min(-1)). In the reperfusion phase, the CBF increased to 51 (45-54) ml 100 g(-1) min(-1), whereas the CMRO2 remained unchanged at 1.1 (1.0-2.5) ml 100 g(-1) min(-1). The CVR decreased from 2.0 mm Hg (1.4-2.1) to 1.4 (1.1-1.8) mm Hg(-1) min 100 g ml. In the anhepatic phase, mean arterial pressure decreased from 92 mm Hg (84-98) to 85 (80-92) mm Hg and at reperfusion it was 80 (71-105) mm Hg. From the anhepatic to the reperfusion phase, the CBF increased 7% (0 to 26) for each mm Hg concomitant increase in PaCO2. The CBF to Vmean ratio remained stable (1.0 [0.8-1.2] vs. 0.9 [0.7-1.1] ml 100 g(-1) min(-1) cm(-1) sec). CONCLUSION During the reperfusion phase of liver transplantations, cerebrovascular dilatation uncouples cerebral oxidative metabolism from blood flow. The increase in CBF is beyond what can be explained by changes in arterial carbon dioxide tension and arterial pressure.

Circulating levels of vasoactive peptides in patients with acute bacterial meningitis

PurposeThe underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g. calcitonin-gene related peptide (CGRP), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1), all of which may be affected by therapeutic interventions used in the intensive care unit. We measured arterial levels as well as the net cerebral flux of these peptides in patients with ABM, and in healthy volunteers undergoing interventions relevant to intensive care.MethodsSeven patients with severe ABM and sepsis and fifteen healthy volunteers were included after informed consent. The net cerebral fluxes of vasoactive peptides were measured by the Kety-Schmidt technique in ABM patients (baseline study only), as well as in volunteers at baseline, during voluntary hyperventilation, after an intravenous injection of lipopolysaccharide (LPS), and during norepinephrine infusion.ResultsThe arterial levels of CGRP, but not of VIP or ET-1, were elevated in patients with ABM, but no net cerebral flux was present. CGRP levels decreased during hyperventilation and after LPS injection. No net cerebral flux of VIP occurred in any group at any time. A cerebral efflux of ET-1, which occurred in volunteers at baseline, was neither present in volunteers after LPS injection nor in patients with ABM.ConclusionThe arterial concentration of the vasodilatory peptide, CGRP, but of neither VIP nor the vasoconstrictor ET-1, is elevated in patients with ABM and sepsis. A constitutive cerebral output of ET-1 appears to be present in healthy humans, but is abolished after LPS injection.

Circulating levels of neuropeptides (cgrp, vip, npy) in patients with fulminant hepatic failure

The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant hepatic failure (FHF). Sixteen patients with FHF were studied and compared to six patients with cirrhosis of the liver. CBF was measured by the (133)Xe wash-out technique. Blood samples were obtained simultaneously from the artery and internal jugular bulb. Concentrations of CGRP and VIP were higher in FHF than in cirrhosis, 87 (55-218) vs. 29 (21-42) pmol/L, and 11 (6-29) vs. 5 (3-9)pmol/L, respectively. NPY was normal, none of the measures were related to CBF, and there was no detectable net brain fluxes. Hyperventilation did not alter any of the measures. CGRP and VIP in FHF seem to reflect hemodynamic changes in the systemic rather than in the cerebral circulation.