Jan C. ter Maaten

Microvascular function relates to insulin sensitivity and blood pressure in normal subjects.

BACKGROUND A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique. METHODS AND RESULTS Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r=-0.50, P<0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity (r=0.84, P<0.001; r=0.78, P<0.001, respectively), and capillary recruitment was inversely related to 24-hour SBP (r=-0.53, P<0.05). Waist-to-hip ratio showed strong associations with insulin sensitivity, blood pressure, and the measures of microvascular function but did not confound the associations between these variables. Subsequent regression analysis showed that the association between insulin sensitivity and blood pressure was not independent of the estimates of microvascular function, and part of the variation in both blood pressure (R2=38%) and insulin sensitivity (R2=71%) could be explained by microvascular function. CONCLUSIONS Insulin sensitivity and blood pressure are associated well within the physiological range. Microvascular function strongly relates to both, consistent with a central role in linking these variables.

Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction

Capillary rarefaction occurs in many tissues in patients with essential hypertension and may contribute to an increased vascular resistance and impaired muscle metabolism. Rarefaction may be caused by a structural (anatomic) absence of capillaries, functional nonperfusion, or both. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of subjects with essential hypertension. We examined skin capillary density with video microscopy before and during maximization of the number of perfused capillaries by venous congestion (structural capillary number) and before and during postocclusive reactive hyperemia (capillary recruitment, which may have a structural and/or functional basis). The study group was composed of 26 patients with never-treated essential hypertension and 26 normotensive control subjects. In both groups, intermittently perfused capillaries in the resting state were an important functional reserve for recruitment during postocclusive hyperemia. Recruitment of perfused capillaries during postocclusive reactive hyperemia was decreased in the hypertensive subjects compared with normotensive control subjects (47.9±6.8 versus 55.3±8.2 capillaries/mm2, respectively;P <0.01). During venous occlusion, maximal capillary density was significantly lower in the hypertensive subjects than in the control subjects (52.5±6.6 versus 57.2±8.6 capillaries/mm2, respectively;P <0.05), suggesting structural rarefaction. However, in the hypertensive subjects compared with the normotensive subjects, a smaller proportion of the maximal number of capillaries was perfused during postocclusive hyperemia (91.6±7.5% versus 97.2±2.7%, respectively;P <0.05), suggesting an additional functional impairment of capillary recruitment. If the difference in capillary numbers during venous congestion (≈4.6 capillaries/mm2) truly reflects the structural difference between the normotensive and hypertensive subjects, then, at most, 62% (4.6/7.4×100%) of the difference in capillary numbers during postocclusive hyperemia (≈7.4 capillaries/mm2) can be explained by structural defects, and at least 38% can be explained by functional defects. In conclusion, in patients with essential hypertension, recruitment of perfused capillaries is impaired, which can be explained by both functional and structural rarefaction.

Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions

OBJECTIVE In patients with essential hypertension, defects in both the metabolic and vascular actions of insulin have been described. Impaired microvascular function, a well-established abnormality in essential hypertension, may explain part of these defects. In the present study we investigated whether microvascular function is impaired in essential hypertension and relates to insulins metabolic and vasodilatatory actions. METHODS We measured 24-h ambulatory blood pressure, capillary recruitment after arterial occlusion, and skin blood flow responses to iontophoresis of acetylcholine and sodium nitroprusside in 18 subjects with untreated essential hypertension and in 18 control subjects. Whole body insulin sensitivity and leg insulin-mediated vasodilatation were assessed with the hyperinsulinaemic clamp technique and plethysmography. RESULTS Hypertensive, as compared to normotensive, subjects had a decreased insulin sensitivity (0.8+/-0.3 vs. 1.7+/-0. 6 mgkg(-1)min(-1) per pmoll(-1); P<0.001), capillary recruitment after arterial occlusion (21.5+/-5.8 vs. 45.9+/-10.4%; P<0.001), acetylcholine-mediated vasodilatation (331+/-84 vs. 688+/-192%; P<0. 001), and insulin-mediated vasodilatation (median 29.3 vs. 47.2%; P<0.05). Correlation analyses with adjustment for sex, age, body mass index and waist-to-hip ratio showed significant relationships of capillary recruitment after arterial occlusion with blood pressure (r=-0.68; P<0.01), insulin sensitivity (r=+0.55; P<0.01) and insulin-mediated vasodilatation (r=+0.51; P<0.05), which extended from the normotensive to the hypertensive range. CONCLUSION Skin microvascular function is associated with blood pressure and insulins metabolic and vasodilatatory actions, both in normotensive and hypertensive subjects. These findings offer a potential mechanistic explanation of the links among insulin resistance, impaired insulin-mediated vasodilatation and hypertension.

The potential role of adenosine in the pathophysiology of the insulin resistance syndrome

An increased intracellular availability of the co-enzyme A esters of long-chain fatty acids is thought to underlie many aspects of the insulin resistance syndrome. However, the cause of clustering of a hyperdynamic circulation, sympathetic activation, hypertension, hyperuricaemia, and a raised haematocrit in the insulin resistance syndrome remains to be elucidated. We propose a mechanism that expands the etiological role of long-chain fatty acids. By inhibiting adenine nucleotide translocators, elevated intracellular concentrations of the co-enzyme A esters of long-chain fatty acids impair mitochondrial oxidative phosphorylation. This is expected to result in a chronic systemic increase in extracellular adenosine concentrations. As adenosine stimulates the sympathetic nervous system, induces systemic vasodilatation, stimulates erythropoiesis, and induces renal vasoconstriction with renal sodium retention, increased extracellular ADO concentrations may be the common denominator explaining the above-mentioned and still unexplained phenomena associated with the insulin resistance syndrome. Along the same lines, hyperuricaemia can be explained by the fact that adenosine is broken down to urate and because of increased renal urate retention.

Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men

Long‐term GH treatment in GH‐deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone.

Oxygen therapy for sepsis patients in the emergency department: a little less?

Liberal oxygen therapy has been a cornerstone in the treatment of critically ill patients. Recently, awareness of hyperoxia toxicity has emerged. We investigated the partial pressure of oxygen in arterial blood (PaO2) in sepsis patients admitted to the emergency department treated with a reduced inspired oxygen fraction of 0.4 instead of 0.6–0.8. A prospective pilot study was carried out over a 3-month period. Patients admitted with two or more SIRS criteria and a suspicion of infection were included. They received 10 l O2/min through a VentiMask 40%. Of 83 patients, 77 had a PaO2 greater than 9.5 kPa with 10 l O2/min, of whom 51 had hyperoxia. Six patients showed hypoxia with 10 l O2/min. Of the hyperoxic patients, 8% died in hospital versus 6% with normoxia. Less than 8% of patients had hypoxia with 10 l O2/min; 66% were hyperoxic. Titration of oxygen therapy to normoxia in the emergency department should be evaluated.

Sepsis patients in the emergency department: stratification using the Clinical Impression Score, Predisposition, Infection, Response and Organ dysfunction score or quick Sequential Organ Failure Assessment score?

Objective The aim of this study was to compare the stratification of sepsis patients in the emergency department (ED) for ICU admission and mortality using the Predisposition, Infection, Response and Organ dysfunction (PIRO) and quick Sequential Organ Failure Assessment (qSOFA) scores with clinical judgement assessed by the ED staff. Patients and methods This was a prospective observational study in the ED of a tertiary care teaching hospital. Adult nontrauma patients with suspected infection and at least two Systemic Inflammatory Response Syndrome criteria were included. The primary outcome was direct ED to ICU admission. The secondary outcomes were in-hospital, 28-day and 6-month mortality, indirect ICU admission and length of stay. Clinical judgement was recorded using the Clinical Impression Scores (CIS), appraised by a nurse and the attending physician. The PIRO and qSOFA scores were calculated from medical records. Results We included 193 patients: 103 presented with sepsis, 81 with severe sepsis and nine with septic shock. Fifteen patients required direct ICU admission. The CIS scores of nurse [area under the curve (AUC)=0.896] and the attending physician (AUC=0.861), in conjunction with PIRO (AUC=0.876) and qSOFA scores (AUC=0.849), predicted direct ICU admission. The CIS scores did not predict any of the mortality endpoints. The PIRO score predicted in-hospital (AUC=0.764), 28-day (AUC=0.784) and 6-month mortality (AUC=0.695). The qSOFA score also predicted in-hospital (AUC=0.823), 28-day (AUC=0.848) and 6-month mortality (AUC=0.620). Conclusion Clinical judgement is a fast and reliable method to stratify between ICU and general ward admission in ED patients with sepsis. The PIRO and qSOFA scores do not add value to this stratification, but perform better on the prediction of mortality. In sepsis patients, therefore, the principle of ‘treat first what kills first’ can be supplemented with ‘judge first and calculate later’.

The value of the clinical impression in recognizing and treating sepsis patients in the emergency department

Objectives Immediate bedside recognition of sepsis in the emergency department (ED) enables early treatment. This study aims to investigate whether the clinical impression score of different health care providers (a) is a good predictor of the severity of sepsis, (b) is mutually agreed, and (c) correlates with the treatment provided in the ED. Methods We performed a prospective observational study in the ED of a tertiary teaching hospital over a 3-month period. The vital signs of all patients of at least 18 years presenting with suspected infection or sepsis were measured on arrival at the ED. In patients with at least one of the ‘Systemic Inflammatory Response Syndrome’ criteria, the nurse, resident, and attending physician assigned a clinical impression score for the degree of acute illness, ranging from 1 (not ill) to 10 (extremely ill). Additional information collected included demographic and treatment data. Results We included 123 patients with sepsis and 11 patients with a (suspected) infection with one ‘Systemic Inflammatory Response Syndrome’ criterion. The clinical impression scores of all health care providers increased significantly between the infection without sepsis, mild sepsis, and severe sepsis groups. The agreement between the health care providers ranged from moderate to good (weighted &kgr; 0.54–0.62). The clinical impression score correlated with time to antibiotics (R=−0.33, P=0.001), amount of volume therapy (R=0.61–0.64, P⩽0.001), and amount of oxygen therapy (R=0.58–0.63, P⩽0.001). Conclusion The clinical impression score is associated with the severity of sepsis, is mutually agreed between the different health care providers and is correlated with sepsis treatment provided in the ED.

Should we start and continue growth hormone (GH) replacement therapy in adults with GH deficiency

During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated on a wide scale, but patients do not profit equally from this expensive therapy. The decision to start and continue GH replacement should be made individually for each patient. An eligible patient should have a clear diagnosis of GHD. In addition, GH replacement therapy should be efficacious. Especially, the unique and valuable effects of GH replacement on exercise performance and quality of life are strong arguments in favour of continuation of therapy. In osteopenic patients, GH replacement increases bone mass. Also, GH induces improvements in the cardiovascular risk profile. However, it has not yet been proved whether GH replacement reduces the incidence of bone fractures and cardiovascular mortality and imp...During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated on a wide scale, but patients do not profit equally from this expensive therapy. The decision to start and continue GH replacement should be made individually for each patient. An eligible patient should have a clear diagnosis of GHD. In addition, GH replacement therapy should be efficacious. Especially, the unique and valuable effects of GH replacement on exercise performance and quality of life are strong arguments in favour of continuation of therapy. In osteopenic patients, GH replacement increases bone mass. Also, GH induces improvements in the cardiovascular risk profile. However, it has not yet been proved whether GH replacement reduces the incidence of bone fractures and cardiovascular mortality and improves life expectancy. Thus far, long-term physiological GH replacement does not appear to be complicated by adverse effects. Therefore, available evidence warrants continuation of long-term GH replacement therapy in patients with a clear-cut diagnosis of GHD who demonstrate beneficial effects of this therapy, especially with regard to exercise performance and quality of life.

Mechanical cardiopulmonary resuscitation in in-hospital cardiac arrest : a systematic review

With increasing rates of in-hospital cardiac arrest, improving resuscitation outcomes is essential. Mechanical chest compressors seem to be related to improved outcome in out-of hospital cardiac arrest; however, the literature on its use in in-hospital cardiac arrest is scarce. We used the Medline public database to systematically review patient outcomes considering mechanical cardiopulmonary resuscitation in in-hospital cardiac arrest. Fourteen studies were found, most cases (n=17), three cohort studies, a clinical pilot study and a registry study. The reported survival rate was high (35 out of 89 patients, 39%) and full neurological recovery was described in 91% of the survivors. Two studies did not report survival rates. Especially in patients with in-hospital cardiac arrest because of treatable causes, early start of mechanical chest compressions could improve future patient outcomes because of better (coronary and brain) perfusion during mechanical chest compressions compared with manual chest compressions. However, the current literature is probably influenced by publication bias and more high-quality research is needed.