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Biomedical subjects

F S Larsen

Publications and source records attributed to F S Larsen.

At least 19 recordsLinked to original sources
PubMed1999

Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high-volume plasmapheresis.

Liver failure represents a major therapeutic challenge, and yet basic pathophysiological questions about hepatic perfusion and oxygenation in this condition have been poorly investigated. In this study, hepatic blood flow (HBF) and splanchnic oxygen delivery (DO2, sp) and oxygen consumption (VO2,sp) were assessed in patients with liver failure defined as hepatic encephalopathy grade II or more. Measurements were repeated after high-volume plasmapheresis (HVP) with exchange of 8 to 10 L of plasma. HBF was estimated by use of constant infusion of D-sorbitol and calculated according to Fick's principle from peripheral artery and hepatic vein concentrations. In 14 patients with acute liver failure (ALF), HBF (1.78 +/- 0.78 L/min) and VO2,sp (3.9 +/- 0.9 mmol/min) were higher than in 11 patients without liver disease (1.07 +/- 0.19 L/min, P <.01) and (2.3 +/- 0.7 mmol/min, P <.001). In 9 patients with acute on chronic liver disease (AOCLD), HBF (1.96 +/- 1.19 L/min) and VO2,sp (3.9 +/- 2.3 mmol/min) were higher than in 18 patients with stable cirrhosis (1.00 +/- 0.36 L/min, P <.005; and 2.0 +/- 0.6 mmol/min, P <.005). During HVP, HBF increased from 1.67 +/- 0.72 to 2.07 +/- 1.11 L/min (n=11) in ALF, and from 1.89 +/- 1.32 to 2.34 +/- 1.54 L/min (n=7) in AOCLD, P <.05 in both cases. In patients with ALF, cardiac output (thermodilution) was unchanged (6.7 +/- 2.5 vs. 6.6 +/- 2.2 L/min, NS) during HVP. Blood flow was redirected to the liver as the systemic vascular resistance index increased (1,587 +/- 650 vs. 2, 020 +/- 806 Dyne. s. cm-5. m2, P <.01) whereas splanchnic vascular resistance was unchanged. In AOCLD, neither systemic nor splanchnic vascular resistance was affected by HVP, but as cardiac output increased from 9.1 +/- 2.8 to 10.1 +/- 2.9 L/min (P <.01) more blood was directed to the splanchnic region. In all liver failure patients treated with HVP (n=18), DO2,sp increased by 15% (P <.05) whereas VO2,sp was unchanged. Endothelin-1 (ET-1) and ET-3 were determined before and after HVP. Changes of ET-1 were positively correlated with changes in HBF (P <.005) and VO2,sp (P <.05), indicating a role for ET-1 in splanchnic circulation and oxygenation. ET-3 was negatively correlated with systemic vascular resistance index before HVP (P <.05) but changes during HVP did not correlate. Our data suggest that liver failure is associated with increased HBF and VO2, sp. HVP further increased HBF and DO2,sp but VO2,sp was unchanged, indicating that splanchnic hypoxia was not present.

Acute Disease↗
PubMed1999

Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration.

Cerebral edema leading to cerebral herniation (CH) is a common cause of death in acute liver failure (ALF). Animal studies have related ammonia with this complication. During liver failure, hepatic ammonia removal can be expected to determine the arterial ammonia level. In patients with ALF, we examined the hypotheses that high arterial ammonia is related to later death by CH, and that impaired removal in the hepatic circulation is related to high arterial ammonia. Twenty-two patients with ALF were studied retrospectively. In addition, prospective studies with liver vein catheterization were performed after development of hepatic encephalopathy (HE) in 22 patients with ALF and 9 with acute on chronic liver disease (AOCLD). Cerebral arterial-venous ammonia difference was studied in 13 patients with ALF. In all patients with ALF (n = 44), those who developed CH (n = 14) had higher arterial plasma ammonia than the non-CH (n = 30) patients (230 +/- 58 vs. 118 +/- 48 micromol/L; P <. 001). In contrast, galactose elimination capacity, bilirubin, creatinine, and prothrombin time were not different (NS). Cerebral arterial-venous differences increased with increasing arterial ammonia (P <.001). Arterial plasma ammonia was lower than hepatic venous in ALF (148 +/- 73 vs. 203 +/- 108 micromol/L; P <.001). In contrast, arterial plasma ammonia was higher than hepatic venous in patients with AOCLD (91 +/- 26 vs. 66 +/- 18 micromol/L; P <.05). Net ammonia release from the hepatic-splanchnic region was 6.5 +/- 6. 4 mmol/h in ALF, and arterial ammonia increased with increasing release. In contrast, there was a net hepatic-splanchnic removal of ammonia (2.8 +/- 3.3 mmol/h) in patients with AOCLD. We interpret these data that in ALF in humans, vast amounts of ammonia escape hepatic metabolism, leading to high arterial ammonia concentrations, which in turn is associated with increased cerebral ammonia uptake and CH.

Acute Disease↗
PubMed1998

Single-dose pharmacokinetics of citalopram in patients with moderate renal insufficiency or hepatic cirrhosis compared with healthy subjects.

OBJECTIVE: To compare the pharmacokinetics of the antidepressant citalopram and its metabolites demethylcitalopram and didemethylcitalopram in subjects with moderate renal insufficiency and subjects with hepatic cirrhosis with that in healthy subjects. METHODS: Pharmacokinetic parameters from three individual, open-label, phase I trials were derived following single oral or intravenous citalopram dose (40 mg) to healthy subjects and a single oral dose (20 mg) to patients. Serum and urine concentrations of citalopram and metabolites were determined using a validated HPLC method. RESULTS: The absolute bioavailability of citalopram tablets in healthy subjects was 80%. The renal clearance was a minor component (<20%) of the total elimination of citalopram. Serum Cmax and t(max) for citalopram were essentially unaffected by the occurrence of renal or hepatic disease. In comparison with healthy subjects, renal impairment was associated with a significant reduction in the renal elimination of citalopram and its two metabolites and a slight prolongation of serum citalopram t1/2 (49.5 h vs 36.8 h in healthy subjects). Cirrhosis resulted in significant decrease in citalopram CLoral (0.21 vs 0.331 x h(-1) x kg(-1) in healthy subjects) and increase in Vz x f(-1) with an approximately twofold increase in t1/2 (83.4 h vs 36.8 h in healthy subjects). Indices of renal (creatinine or 51Cr-EDTA clearances) and hepatic (galactose elimination capacity or Child-Pugh score) function were poor predictors of the changes in the pharmacokinetics of citalopram and its metabolites in these populations. CONCLUSION: No reduction of citalopram dosage is warranted in patients with moderately impaired renal function. However, that may not apply for patients with severe renal failure. In patients with impaired hepatic function, prescription of a lower dosage of citalopram may be appropriate.

Administration, Oral↗
PubMed1998

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.

Adult↗
PubMed1997

Liver function, cerebral blood flow autoregulation, and hepatic encephalopathy in fulminant hepatic failure.

In acute liver failure, massive hepatic necrosis may result in impaired regulation of cerebral blood flow (CBF), development of encephalopathy, and cerebral edema. In 10 consecutive patients with fulminant hepatic failure (FHF), CBF autoregulation was found to be absent, as transcranial Doppler mean flow velocity (Vmean) in the middle cerebral artery increased from 49 (27-59) to 69 (49-92) cm/s (P < .05) during a 30- (28-34) mm Hg rise in mean arterial pressure (MAP). In 7 patients, restoration of CBF autoregulation was shown within 48 (24-120) hours after spontaneous hepatic recovery or liver transplantation, before complete alleviation of hepatic encephalopathy (HE). The extraordinarily rapid restoration of CBF autoregulation in patients with FHF following re-establishment of liver function is unique compared with other conditions affecting the CBF autoregulation, indicating a close connection between liver function and regulation of cerebral circulation. Because CBF autoregulation was restored after initial alleviation of HE, it does not appear to be of major pathophysiological importance in the mediation of HE.

Adult↗
PubMed1997

Indomethacin normalizes intracranial pressure in acute liver failure: a twenty-three-year-old woman treated with indomethacin.

In patients with acute liver failure, cerebral herniation is a common cause of death. The present study reports the effect of indomethacin on four occasions of intracranial hypertension, in a 23-year old previously healthy woman with severe acetaminophen poisoning. During each episode of intracranial hypertension, the patient was treated with 25 mg of indomethacin, and each time the intracranial pressure normalized. We recommend further controlled studies to determine the exact effect of indomethacin on cerebral blood flow and metabolism before it is recommended for treatment of intracranial hypertension in patients with acute liver failure.

Acute Disease↗
PubMed1997

Haemodynamic changes after high-volume plasmapheresis in patients with chronic and acute liver failure.

OBJECTIVE: To evaluate the haemodynamic changes during treatment with high-volume plasmapheresis in patients with chronic liver failure compared to patients with acute liver failure. METHODS: Haemodynamic measurements were performed with a Swan-Ganz catheter and thermodilution technique. High-volume plasmapheresis (mean plasma exchange of 8.6 litres) was performed in 11 patients with chronic and 16 patients with acute liver failure. RESULTS: In patients with chronic liver failure, systemic vascular resistance index was unaltered: 1193 +/- 494 dynscm-5m2 before treatment versus 1180 +/- 399 dynscm-5m2 after. Mean arterial pressure increased from 69 +/- 11 mmHg to 78 +/- 13 mmHg (P < 0.05) and cardiac output increased from 8.1 +/- 2.4 l/min to 8.9 +/- 2.4 l/min (P < 0.05) during high-volume plasmapheresis. In patients with acute liver failure, systemic vascular resistance index increased from 1154 +/- 628 dynscm-5m2 to 1614 +/- 738 dynscm-5m2 (P < 0.001). In this group mean arterial pressure increased from 78 +/- 16 mmHg to 95 +/- 10 mmHg (P < 0.001) and cardiac output decreased from 9.6 +/- 3.7 l/min to 8.2 +/- 2.9 l/min (P < 0.01). CONCLUSION: The hyperkinetic circulation in chronic and acute patients was differently affected by high-volume plasmapheresis. We suggest that in chronic liver failure both portosystemic shunting and chronic peripheral vasodilation may contribute to the hyperkinetic syndrome, whereas in acute liver failure a humoral factor which can be removed by high-volume plasmapheresis is a main contributor.

Acute Disease↗
PubMed1997

Oral terbinafine in toenail dermatophytosis. A double-blind, placebo-controlled multicenter study with 12 months' follow-up.

The treatment of onychomycosis has previously often been protracted and unsuccessful. Terbinafine has been shown to be effective in short-term regimens. In this double-blind, placebo-controlled study, 148 patients with toenail dermatophytosis were randomized to treatment with either 250 mg terbinafine daily or placebo for 3 months. An additional treatment was given for 3 months to patients whose infection had not responded. The patients were followed clinically and mycologically through 12 months. After 3 months 82% of the terbinafine-treated group, versus 5% of the placebo group, showed significant improvement, i.e. negative culture and growth of unaffected nail more than 2 mm (p = < 0.0001). After 12 months clinical and mycological cure was seen in 40% of the patients treated with terbinafine for 3 or 6 months, while 67-81% were clinically cured, but with positive microscopy. Side-effects occurred in 13.5% of the terbinafine group, versus 5.4% of the placebo group, and were mild. 250 mg terbinafine daily for 3 months was significantly more effective than placebo. The efficacy did not appear to improve with additional treatment for 3 months.

Administration, Oral↗
PubMed1996

Preservation of cerebral oxidative metabolism in fulminant hepatic failure: an autoregulation study.

Under normal conditions cerebral blood flow (CBF) is regulated to secure oxidative brain metabolism, but in patients with fulminant hepatic failure (FHF), insufficient CBF has been suggested to precede cerebral edema and intracranial hypertension. In order to determine if insufficient CBF and hypoxia are present in patients with FHF we increased the mean arterial pressure and measured cerebral metabolism. In six patients with FHF CBF determined by 133Xenon injection technique, transcranial Doppler mean flow velocity in the middle cerebral artery (Vmean) and cerebral metabolism were determined, before and after an increase in mean arterial pressure by norepinephrine infusion. Mean arterial pressure was measured in a radial artery, and blood samples from the radial artery and internal jugular vein allowed calculation of the cerebral arteriovenous oxygen (AVDO2), -glucose (AVDgl), and -lactate (AVDlac) differences. Cerebral metabolic rates (CMRO2,-gl,-lac) were calculated as AVDO2,-gl,-lac times CBF. Mean arterial pressure was raised from 70 (54-105) to 111 (93-128) mm Hg during intravenous infusion of norepinephrine. CBF increased from 34 (12-55) to 47 (27-81) mL . 100g-1. min-1 (p < 0.05) and Vmean from 53 (42-60) to 67 (61-79) cm.s-1 (p < 0.05), whereas CMRO2 (1.4 (0.9-2.4) mL . 100g-1 . min-1), CMRgl (11 (4.8-20) mumol 100g-1 . min-1), and CMRlac (3.2 (0-8.9) mumol . 100g-1 . min-1) remained unchanged. Our finding indicates that cerebral oxidative metabolism is preserved in patients with FHF. Cerebral autoregulation is absent, however, and neuroprotective critical care is suggested to be guided by internal jugular vein oxygen saturation to secure appropriate cerebral oxygenation.

Adolescent↗
PubMed1996

Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia.

BACKGROUND/AIMS: Normally, cerebral blood flow responds to changes in the arterial carbon dioxide tension (PaCO2) but not to changes in mean arterial pressure, commonly referred to as the cerebral CO2-reactivity and autoregulation. In patients with fulminant hepatic failure and in the rat with thioacetamide-induced liver failure, autoregulation is absent, presumably due to cerebral vasoparalysis. Since also CO2-reactivity may then be compromised, it was studied in patients with fulminant hepatic failure and rats with thioacetamide-induced liver failure. METHODS: In ten patients (median age 32 (range 20-48) years)) and in ten age-matched volunteers, cerebral perfusion was elevated by transcranial Doppler assessed mean flow velocity (V(mean)) in the middle cerebral artery during hypo- and hyper-capnia. In six rats with liver failure and in six control rats, cerebral blood flow was measured repeatedly by the intracarotid 133 Xenon injection technique. RESULTS: In the patients and volunteers, PaCO2 was lowered from 33 (23-44) to 28 (23-39) mmHg by hypocapnia and raised to 40 (34-48) mmHg by hypercapnia or 5% CO2 inhalation. During hypocapnia, the CO2-reactivity did not differ significantly between patients and volunteers, 4.0 (1.1-7.4) vs. 3.0 (1.7-5.0)% mmHg(-1), while it was reduced during hypercapnia in the patients, 2.2 (1.8-5.2) vs. 4.6 (3.0-8.0)% mmHg(-1) (p < 0.05). In the rats, PaCO2 was reduced from 39 (37-40) to 30 (29-31) mmHg and then raised to 51 (41-55) mmHg. During hypocapnia, CO2-reactivity was similar in rats with liver failure and in control rats, 2.3 vs 2.7% mmhg(21), respectively. In all rats with liver failure CO2-reactivity was abolished during hypercapnia, while it was 1.5% mmHg(-1) in the control rats (p < 0.01). CONCLUSIONS: The finding that cerebral CO2 reactivity is reduced in hypercapnia, while it is preserved in hypocapnia, suggests that gradual dilation of the cerebral resistance vessels develops in fulminant hepatic failure and connects previous morphological studies with changes in the regulation of cerebral blood flow, i.e. impaired cerebral autoregulation and blunted CO2-reactivity.

Acute Disease↗
PubMed1996

Validation of transcranial near-infrared spectroscopy for evaluation of cerebral blood flow autoregulation.

The aim of the study was to evaluate a new noninvasive transcranial near-infrared spectroscopy (TNIRS) technique for determination of the lower limit of cerebral blood flow (CBF) autoregulation by comparing this technique with the standard cerebral arteriovenous oxygen saturation difference (AVDo2) method. In eight healthy volunteers, mean arterial blood pressure was increased by infusion of angiotensin and decreased by the combination of lower-body negative pressure and labetalol. For each 5-mm Hg change in mean arterial pressure, blood was sampled from the bulb of the internal jugular vein and a radial artery, and simultaneously, the oxygen saturation of hemoglobin in the brain was measured with an INVOS 3100 Cerebral Oximeter (Somanetics). The lower limit of autoregulation was then calculated by a computer using (a) AVDo2 and (b) the difference between arterial oxygen saturation and the saturation determined with the cerebral oximeter (ACDo2). The median lower limit of autoregulation determined by the two methods was 73 and 78.5 mm Hg, respectively (p > 0.05). A statistically significant correlation between relative CBF (percentage of baseline) determined with the two methods was found below the lower limit of autoregulation (1/AVDo2 = 12 + 0.8 x 1/ACDo2; r = 0.55; p < 0.001). For all the 98 pairs of saturations registered, the correlation was 0.37 (p < 0.001), the mean difference was 16%, and the limits of agreement were -2.2 and 33.8%. We conclude that the cerebral oximeter might be useful in evaluation of the lower limit of cerebral autoregulation. This method, however, is of no value for estimation of levels of global cerebral oxygen saturation.

Adult↗
PubMed1996

Cerebral blood flow, oxygen metabolism and transcranial Doppler sonography during high-volume plasmapheresis in fulminant hepatic failure.

OBJECTIVE: The effect of high-volume plasmapheresis on hepatic encephalopathy, cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) was investigated in patients with fulminant hepatic failure (FHF). METHODS: Twelve consecutive patients (8 women, 4 men, median age 34 years (range 19-51), were studied before and after high-volume plasmapheresis with 10-16 litres fresh frozen plasma, while PaCO2 and body temperature were maintained at 30 (23-34) mmHg and 37.6 degrees C (36.6-38.4), respectively. Blood samples from the internal jugular vein and a radial artery allowed calculation of the cerebral arteriovenous oxygen difference (AVDO2) and oxygen extraction (AVDO2 divided by arterial oxygen content). CBF was determined by a xenon-133 clearance method in eight patients and CMRO2 calculated as AVDO2 times CBF. Cerebral perfusion pressure (CPP) was determined as the difference between mean arterial and subdural pressures in eight patients. RESULTS: High-volume plasmapheresis was initiated 22 (6-168) h after the development of hepatic encephalopathy and 11 patients had grade 4 encephalopathy. Following high-volume plasmapheresis the grade of encephalopathy improved in four patients. The CBF increased from a median of 31 (16-86) to 45 (18-97) ml/100 g/min and as oxygen extraction remained unchanged (32 (9-41) vs. 29 (7-39)%), CMRO2 increased from 1.24 (0.96-1.82) to 1.86 (1.00-2.07) ml/100 g/min (P < 0.05). The CPP increased from 62 (19-76) to 92 (50-105) mmHg (P < 0.01), whereas the intracranial pressure remained unchanged (19 (3-45) vs. 11 (5-33) mmHg). No statistical difference was found between the relative changes in the above parameters in survivors compared to non-survivors. CONCLUSION: Although the clinical status did not improve in all patients, both CBF and CMRO2 increased after high-volume plasmapheresis. The alleviation of brain oxygen metabolism by high-volume plasmapheresis may reflect partial removal of neuroinhibitory plasma factors.

Adult↗
PubMed1996

Atopic dermatitis may be linked to whether a child is first- or second-born and/or the age of the mother.

Five hundred and thirty families with at least 1 child who had been referred to a dermatologist with atopic dermatitis were interviewed in an effort to determine whether factors such as the age of the mother when a child is born and/or birth rank can contribute to the development of atopic dermatitis. The families interviewed had a total of 1,084 children, or an average of 2 children per family. Sixty per cent of the children with atopic dermatitis were under 5 years of age. Ninety-one per cent of them had developed the disease before the age of 3; those most severely affected had developed the disease during the first year of life. In families with 2 children, but only 1 child with atopic dermatitis, the odds ratio for the second child to develop atopic dermatitis was 1.379 (0.025 < p < 0.05). The average maternal age was 24.8 to 25.2 years when giving birth to the first child and 28 years when giving birth to the second child, irrespective of the status of the child. Thus, atopic dermatitis can be related to birth rank or to the age of the mother.

Adult↗
PubMed1995

[Paracetamol poisoning at a department of hepatology].

In this retrospective study we evaluated the frequency of complications in 108 patients with acetaminophen poisoning admitted to the Department of Hepatology, Rigshospitalet, Copenhagen from 1.10.1990-30.9.1993. Twenty-five patients (23%) developed hepatic encephalopathy grade II-IV, with a survival rate of 44%. In patients who developed grade IV encephalopathy the median time from intoxication to INR > 3.7 was 60 hours. At a median of only five hours later grade II encephalopathy was present, and grade IV at a median of a further 20 hours later. Ninety-three patients were re-evaluated according to the nomogram indicated by Prescott (6). If the initial position was in the "very severe" area the risk of developing encephalopathy was 34% (20-51%), if not the risk was 6% (1-16%). Serum creatinine above 200 microM at admission indicated a risk of hepatic encephalopathy of 64% (35-87%). INR > 1.54 was associated with a 35% risk of hepatic encephalopathy. Patients in the "very severe" area should be referred to a unit where liver transplantation is possible, even if other factors known to indicate poor prognosis are not present.

Acetaminophen↗