AIM: This study described the basic characteristics of children aged 0-16 years who were treated in intensive care units (ICUs) and paediatric ICUs (PICUs), compared their outcomes and examined any causes of death.

METHODS: This was a retrospective cohort study of admissions to 74 ICUs and three PICUs in Sweden that were recorded in the Swedish Intensive Care Registry from January 1, 2008 to December 31, 2012.

RESULTS: We retrieved data on 12 756 children who were admitted 17 003 times. The case mix differed between the ICUs, which were mainly admissions for injuries, accidents and observation, and PICUs, which were mainly admissions for malformations, genetic abnormalities and respiratory problems (p < 0.001). The median stays in the ICUs and PICUs were 1.4 and 3.5 days (p < 0.001), respectively. The respective crude mortality rates were 1.1% and 2.0, and the Paediatric Index of Mortality version 2 standardised mortality ratios were 0.43 and 0.50. None of these differences were significant. Most deaths were within 24 hours: About 57% in the ICUs, mainly from brain anomalies, and 13% in the PICUs, mainly from circulatory problems.

CONCLUSION: Sweden had a low mortality rate in both ICUs and PICUs and the children admitted to these two types of unit differed.

Objective. High doses of the synthetic colloid hydroxyethyl starch (HES) used for plasma expansion have been associated with impaired haemostasis and hypocoagulation. Less is known about effects on clot formation in the low haemodilutional range (less than 40%). This study evaluated the effects of low haemodilution with HES and albumin on coagulation using two different viscoelastic methods. Methods. Clot formation was studied in vitro in healthy donor blood after 10% and 30% haemodilution with 60 g/L HES 130/0.4 or 50 g/L albumin with free oscillation rheometry (FOR) and rotational thromboelastography. Results. Clotting time was not significantly affected at 10% haemodilution but was prolonged with both substances at 30% dilution (p less than 0.01-0.001). The effect was significantly more pronounced with HES than with albumin. The elasticity of the clot was slightly reduced at 10% dilution with albumin, more pronounced at 10% dilution with HES (p less than 0.05), further reduced at 30% dilution with albumin and to a still greater extent at 30% dilution with HES (p less than 0.05). With albumin the functional activity of fibrinogen was not reduced in excess of the dilutional effect. HES in contrast produced a further reduction in clot elasticity than caused by mere dilution at both 10% and 30% dilutions (p less than 0.001). Conclusions. There is an adverse effect on clot formation even at low grade haemodilution with both albumin and HES. The effect on coagulation is significantly more pronounced with HES than with albumin.

Abstract Objective: Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin. Methods: We investigated whether increasing concentrations of norepinephrine (NE, 1.859 mu mol/L) and vasopressin (VP, 1100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate). Results: We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 +/- 1.7 to 10.9 +/- 0.9 mmol/L for the highest concentration of NE (p andlt; 0.001) and from 8.1 +/- 1.4 to 10.0 +/- 1.7 mmol/L for the highest concentration of VP (p = 0.037). Glucose decreased from 2.3 +/- 0.7 to 0.41 +/- 0.18 mmol/L for NE (p = 0.001) and from 2.7 +/- 0.6 to 1.3 +/- 0.5 mmol/L for VP (p andlt; 0.001). Lactate increased from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for NE (p = 0.005) and from 1.1 +/- 0.4 to 2.6 +/- 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters. Conclusions: Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.

Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support. less thanbrgreater than less thanbrgreater thanMethod: Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded. less thanbrgreater than less thanbrgreater thanResults: Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine. less thanbrgreater than less thanbrgreater thanConclusion: These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.

Microdialysis is a well-established technique for continuous sampling of small, water-soluble molecules within the extracellular fluid space in vivo. It also allows the use of microdoses of drugs, and the simultaneous evaluation of their related effects at the site of action. The present study was an experimental, randomized microdose trial to develop a human vascular model of dose response. We aimed to evaluate a microdialysis dosing method using urea clearance as a marker of druginduced changes in dermal blood flow and metabolism (glucose and lactate) in 12 healthy volunteers. We found that asymptomatic vasoconstriction can be detected by continuous microdialysis measurements of urea clearance in dermal tissue. More importantly, dose-effect relations using the E_max model could be constructed using the corresponding data on drug doses and both the urea clearance-based flow estimates and the changes in concentrations of tissue metabolites. This in vivo human experimental skin model offers an interesting tool with which both the dose-response effects on blood flow and concentrations of tissue metabolites of potent vasoactive substances can be evaluated.

Objective: The aim of this study was to evaluate the urea clearance technique for the measurement of drug-induced blood flow changes in human skin, and compare it with two non-invasive techniques: polarization light spectroscopy and laser Doppler perfusion imaging.

Methods: Fifteen microdialysis catheters were placed intracutaneously on the volar aspect of the forearms of healthy human subjects, and were perfused with nitroglycerine, noradrenaline, and again nitroglycerine, to induce local tissue hyperaemia, hypoperfusion, and hyperaemia, respectively.

Results: Urea clearance, but not the other techniques, detected the changes in blood flow during all three periods of altered flow.  The last hyperaemic response was detected by all three methods.

Conclusion: Urea clearance can be used as a relatively simple method to estimate blood flow changes during microdialysis of vasoactive substances, in particular when the tissue is preconditioned in order to enhance the contrast between baseline and the responses to the provocations. Our results support that, in the model described, urea clearance was superior to the optical methods as it detected both the increases and decrease in blood flow, and the returns to baseline between these periods.

To examine to what extent availability of social integration affects health-related quality of life (HRQoL) in former intensive care unit (ICU) patients and how it relates to corresponding findings in a general reference group. Controlled, multicenter, prospective, explorative study. HRQoL data (SF-36) were collected from three combined medical and surgical ICUs in the south-east of Sweden. Social integration was assessed by the Availability of Social Integration (AVSI) instrument (seven questions related to the social interaction of the patient). As reference group, a random sample (n = 6,093) of people from the uptake area of the hospitals was used. Social integration (AVSI), HRQoL (SF-36), and comorbidity were examined also in the reference group. None. The level of social integration significantly affected HRQoL for the former ICU patients, whereas no such effect was seen for the general reference group. For the ICU patients, social integration affected HRQoL to a larger extent than age, sex, and the ICU-related factors examined, but to a lower extent than the pre-existing diseases. For a comprehensive assessment of HRQoL in former ICU patients, it is mandatory to include the effect of social integration.

Patients who require critical care, including those with burns, are affected by a systemic inflammatory reaction, which at times has consequences such as multiple organ dysfunction and failure. It has become increasingly evident that other factors important in the development of organ dysfunction are disturbances at the tissue level, in the microcirculation. Such disturbances activate cascade systems including stress hormones, all of which have local effects on organ function.

Despite this knowledge, monitoring and treatment in critical illness today relies mainly on central haemodynamics and blood sampling.

Microdialysis is a minimally invasive technique that enables us to study the chemical composition and changes in biochemistry in the extracellular, extravascular space in living tissues. Most of our current experience is from animal models, but the technique has also been used in humans and has become routine in many neurosurgical intensive care units to monitor brain biochemistry after severe injury. In skin, this experience is limited. During the first half of this thesis we studied the injured and uninjured skin of severely burned patients. The results show that there are severe local metabolic disturbances in both injured and uninjured skin. Most interesting is a sustained tissue acidosis, which is not detectable in systemic (blood) sampling. We also recorded considerable alterations in the glucose homeostasis locally in the skin, suggesting a cellular or mitochondrial dysfunction. In parallel, we noted increased tissue glycerol concentrations, which indicated appreciable traumainduced lipolysis.

We also examined serotonin kinetics in the same group of patients, as serotonin has been claimed to be a key mediator of the vasoplegia and permeability disturbances found in patients with burns. We have shown, for the first time in humans to our knowledge, that concentrations of serotonin in skin are increased tenfold, whereas blood and urine concentrations are just above normal. The findings support the need for local monitoring of substances with rapid local reabsorption, or degradation, or both. The results also indicate that serotonin may be important for the systemic response that characterises burn injuries.

In the second half of the thesis we evaluated the effects of microdosing in skin on metabolism and blood flow of vasoactive, mainly stress-response-related, drugs by the microdialysis system. The objectives were to isolate the local effects of the drugs to enable a better understanding of the complex relation between metabolic effects and effects induced by changes in local blood flow. In the first of these two studies we showed that by giving noradrenaline and nitroglycerine into the skin of healthy subjects we induced anticipated changes in skin metabolism and blood flow. The results suggest that the model may be used to examine vascular and metabolic effects induced locally by vasoactive compounds. Data from the last study indicate that conventional pharmacodynamic models (E_max) for time and dose response modelling may be successfully used to measure the vascular and metabolic response in this microdosing model.

We conclude that the microdialysis technique can be successfully used to monitor skin metabolism and iso late a mediator (serotonin) of the local skin response in burned patients. It was also feasible to develop a vascular model in skin based on microdialysis to deliver vasoactive substances locally to the skin of healthy volunteers. This model provided a framework in which the metabolic effects of hypoperfusion and reperfusion in skin tissues could be examined further.