Treatment of cefuroxime-induced neurotoxicity with continuous venovenous haemofiltration.

A 61-year-old woman with decreased consciousness, myoclonus, tremors, nystagmus and bradypnoea, due to cefuroxime-induced neurotoxicity, was admitted to the intensive care unit. Continuous venovenous haemofiltration (CVVH) rapidly reduced plasma cefuroxime concentrations and improved neurological manifestations within the next few hours. Retrospective pharmacokinetic assessment showed a total cefuroxime clearance of 166 ml/min during the CVVH.

[Deferred consent for inclusion of patients unable to give their consent in studies in the field of emergency medicine]. / Uitgestelde toestemming voor inclusie van beslissingsonbekwame patiënten in studies van spoedeisende geneeskunde.

Respect for individual autonomy, expressed in the concept of informed consent, is a basic principle in research with humans. Many patients in intensive care are unable to give consent because of mental incapacity, and this can be further complicated in emergency research, in which the treatment or experiment needs to be initiated without delay. In those situations consent can be deferred. Randomization is done without prior consent, followed by patients' or relatives' consent at a later stage. Butwhat should one do with the data if the patient dies at an early stage after randomization before consent could be obtained? Should the data be used or not? Should the relatives be asked for consent for using the data? The Dutch Central Committee on Research involving Human Subjects (CCMO) states that asking for consent after the patient has died makes no sense, because with the death of the patient the research has ended. Relatives do not have the authority to give consent for the use of medical data after the patient has died. Data can be used anonymously in the final analysis of the trial. We propose a flowchart for this procedure.

Candidemia in intensive care unit patients: risk factors for mortality.

Aim of this study was to evaluate whether risk factors which predict the development of candidemia may also predict death in ICU patients with candidemia. During an 8-year-period all ICU patients whose blood cultures yielded Candida species (n = 40) were retrospectively evaluated in a case-control fashion. The average incidence of Candida bloodstream infections was 5.5 per 10,000 patient days, ranging from 2.4 in 1990 to 7.4 in 1994. C. albicans was the most common pathogen in candidemic patients, but the proportion of non-C. albicans strains showed an increasing trend during 1989-1993, with a major shift towards non-C. albicans species in 1994. The overall mortality of patients with candidemia was 58%. Mortality was highest in the group of patients with multi-organ dysfunction syndrome, especially among those in need of hemodialysis. Risk factors for the development of candidemia, such as age, malignancy, steroid use, i.v. catheterization, and the use of broad-spectrum antibiotics were not correlated with mortality in the ICU patients studied.

The microcirculation and hypertension.

AIM: To review published evidence on the effects of arteriolar changes in primary and secondary hypertension. BACKGROUND: Pressure profile analyses have shown that the microcirculation is a major site of vascular resistance. With the recent refinement of intravital microscopy techniques detailed information has become available on mechanisms of the microvascular resistance increase in hypertension. Three mechanisms play an important role: (1) a decrease in arteriolar diameter; (2) arteriolar vessel wall hypertrophy; and (3) small arteriolar and capillary rarefaction. METHOD: The evidence was synthesized into a hypothesis on the role of the microcirculation in primary forms of hypertension. HYPOTHESIS: The hypothesis formulated contains two important elements in that (1) diminished outgrowth of the microvascular bed in different tissues is seen as an important early pathogenic mechanism; and (2) the decreases in arteriolar diameter and vessel wall hypertrophy are seen as adaptive mechanisms that maintain a constant wall stress. The three factors together maintain the increase in vascular resistance that is common to all established forms of primary hypertension.

The microcirculation and essential hypertension.

Essential hypertension is characterized by a progressive increase of the mean arterial pressure paralleled by a concomitant increase in the total peripheral resistance. This elevated resistance is the consequence of (a) a decreased internal diameter, (b) an increased wall-to-lumen ratio or (c) a decreased number of small arteries or arterioles. A considerable part of the elevated vascular resistance is determined at the microcirculatory level. This paper reviews the studies performed to unravel the resistance-elevating mechanisms in the microvasculature of different tissues. Furthermore the possible role of the microcirculation in the pathogenesis of essential hypertension is discussed.

A functional morphometric study of the cremaster muscle microcirculation in young spontaneously hypertensive rats.

Increased vascular resistance in spontaneous hypertension has been attributed to a reduced arteriolar lumen and a decrease in the number of arterioles and capillaries. In the present study, microvascular mechanisms for increased resistance were investigated in the cremaster muscle of 5-6-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) using intravital microscopy. Vessels were classified on the basis of their location in the network relative to their branching order and function (A1-A4). In each preparation, one vessel of each category was observed for its side-branches, using bright-field microscopy. By comparing the number of side-branches seen under control conditions and after maximal vasodilatation (10(-3) mol/l adenosine, topically) we assessed their functional reserve. Capillary density was investigated using incident fluorescence microscopy. Both under control conditions and after vasodilatation, mean arterial pressure and heart rate were increased in SHR (mean arterial pressure: SHR 103 +/- 4 mmHg, WKY 89 +/- 3 mmHg, P less than 0.05; heart rate: SHR 380 +/- 16 beats/min, WKY 343 +/- 12 beats/min, P less than 0.05). Arterioles (A1-A4) of SHR and WKY were equal in diameter (SHR: 75.8 +/- 3.2, 48.7 +/- 1.1, 21.4 +/- 0.9, 10.0 +/- 0.04 microns; WKY: 71.6 +/- 2.4, 48.9 +/- 1.1, 18.5 +/- 0.9, 9.8 +/- 0.3 microns; A1-A4, respectively). After adenosine, the relative increase in diameter was similar in both groups. The number of side-branches under control conditions was similar in A1 and A2 vessels. SHR had fewer A3 vessels per A2 and fewer A4 vessels per A3 (per unit length), indicating a diminished arteriolar reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Microvascular alterations in adult conscious spontaneously hypertensive rats.

The dorsal skin flap technique was used to study skeletal muscle microcirculation in conscious 10-12-week-old spontaneously hypertensive rats and normotensive Wistar-Kyoto control rats. Videorecordings were made for off-line analysis of consecutive segments of the vascular bed. Resting diameters were significantly smaller in spontaneously hypertensive rats than in Wistar-Kyoto rats at the first-order (-28%) and second-order arteriolar (-21%) levels. Precapillary third-order and fourth-order arterioles of spontaneously hypertensive rats had normal diameters, whereas postcapillary small venule diameters were slightly larger in spontaneously hypertensive rats. Thirty percent and 41% of the spontaneously hypertensive rat and Wistar-Kyoto rat third-order arteriolar vessels and 63 and 45% of the fourth-order arteriolar vessels exhibited vasomotion. Vasomotion amplitude, but not frequency, was significantly higher in spontaneously hypertensive rats than in Wistar-Kyoto rats. It is concluded that, in the established phase of spontaneous hypertension in the rat, a decreased diameter of large arterioles is the major mechanism underlying the increased vascular resistance in cutaneous skeletal muscle.

Hypertension, the microcirculation and serotonin.

Essential hypertension in humans and most experimental animal models of hypertension is hemodynamically characterized by an increased vascular resistance. The site of resistance increase has been localized by recent intravital microscopic studies in most vascular beds primarily in the microcirculation, i.e. in arterioles smaller than 150 microns. Three mechanisms are held responsible for the resistance increase: (1) a rarefaction of the smallest arterioles and capillaries, (2) an increased wall to lumen ratio and (3) a decreased internal diameter. The latter two effects have been localized primarily in the larger arterioles and arteries. The contribution of each of the three factors to the rise in total peripheral resistance depends on the vascular bed, the model of hypertension and its stage of development. Serotonin is one of the endogenous mediators of vascular tone. Its effects have thus far been mostly studied in relation to alterations of internal vascular diameter. Larger arterioles and arteries constrict, but resistance-sized smaller arterioles dilate in response to the exogenous application of serotonin.

Microcirculatory changes in cremaster muscle during early spontaneous hypertension in the rat.

The microcirculatory control of flow was studied in the cremaster muscle of 5- to 6-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using intravital microscopic techniques. Arterioles were classified according to a functional branching order from A1-A4 vessels. Capillary architecture was measured in a separate series of experiments. No significant differences were found in the WKY or SHR vessel diameters, with the exception of third-order arterioles, which were slightly, but significantly, larger in SHR. However, the number of A3 and A4 vessels as well as the capillary density was significantly lower in SHR than in WKY. The differences were even more pronounced during maximal vasodilation induced by local application of 10(-3) mol/l adenosine. The data show that rarefaction of small blood vessels rather than decreased arteriolar diameter is an early characteristic of spontaneous hypertension in the rat.

Differential effects of general anesthetics on regional vasoconstrictor responses in the rat.

Although many cardiovascular experiments are performed in the presence of anesthetics, little is known about the depressant effect on regional vascular reactivity. The effect of 2 commonly used anesthetics, pentobarbital (PB) and a chloralose urethane mixture (C-U) on vascular reactivity of different tissues was studied in rats. In order to measure blood flow, rats were equipped with miniaturized Doppler flow probes on the renal artery, the superior mesenteric artery and abdominal aorta. Catheters were implanted for measuring blood pressure and for i.v. injections of differently acting vasopressor substances. Vasoconstriction was induced by i.v. noradrenaline (NA), phenylephrine (P) and angiotensin II (AII), in conscious animals and in anesthetized rats (PB or C-U). The 3 vasopressor substances caused a dose-dependent increase in regional vascular resistances. In anesthetized animals, constrictor responses following P were not affected in any beds. PB diminished the effect of NA and AII in all vascular beds studied, while C-U only depressed renal and splanchnic reactivity. During C-U anesthesia, hindquarter vascular reactivity was not affected. This indicates that anesthetics exert differential regional effects, depending upon the substances studied. This complicates extrapolation of experimental data from one bed to other vascular beds or to conscious animals.

Pharmacological evidence for rapid destruction of efferent renal nerves in rats by intrarenal infusion of 6-hydroxydopamine.

In a previous study we reported that intrarenal (i.r.) infusion of 1 mg 6-hydroxydopamine (6-OHDA) in rats resulted in selective efferent denervation of the infused kidney. Although the vasoconstrictor response to electrical stimulation of the posterior hypothalamus (PH) was already abolished 24 h after infusion, norepinephrine (NE) content of the kidney was reduced by only approximately 50% at that time. In the present study, the status of renal nerves 45 min after infusion of 6-OHDA by i.r. application of scorpion venom (SV), a NE releasing agent, was investigated. In saline pretreated rats, 10 micrograms SV i.r. caused a rapid increase (+355 +/- 80%) in vascular resistance in the injected kidney, whereas only minor changes were observed in resistances of the non-injected kidney, mesentery and hindquarters. Pretreatment of animals with phentolamine (1 mg/kg i.v.) largely abolished the vasoconstrictor response (+57 +/- 20%), confirming dependence of the effect of SV on release of NE from nerve terminals. Finally, pretreatment with 1 mg 6-OHDA i.r. also resulted in abolition of renal vasoconstriction following SV (+7 +/- 6%). The results indicate that as early as 45 min after i.r. infusion of 1 mg 6-OHDA in rats, efferent renal nerve endings are no longer functional.