Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

Influence of the arm position on intra-arterial blood pressure measurement.

The reference level for the measurement of blood pressure (BP) is the level of the right atrium. In practice this is regularly disregarded, as the patient's arm is usually placed lower than the right atrial level. The aim of the study was to determine the influence of first, different arm positions and second, different transducer positions on the intra-arterially (i.a.) recorded BP. In 16 healthy men (age 28.1 +/- 8.0 (s.d.) years), i.a. BP was recorded at the left arm in supine position, using a 5-7 cm long cannula. The baseline position was with the tip of the cannula placed precisely at the level of the right atrium. Subsequently, the following changes were made: 5, 10, 15 and 20 cm above and 5, 10, 15, and 20 cm below the baseline position. A 2-min rest period was allowed in each position before the BP was measured. The whole procedure was done either with the transducer connected to the arm at the place of the cannula (n = 7), or with the transducer placed next to the subject and continuously kept at the right atrial level during the BP measurement (n = 9). Simultaneously, baseline BP was measured indirectly, with a standard mercury sphygmomanometer, in the opposite arm maintained with the cubital fossa at the right atrial level during the whole procedure. This resulted in the first group of seven volunteers for both the i.a. systolic (SBP) and diastolic BP (DBP) values to significantly decrease (P < 0.001) when the arm together with the transducer were elevated above the level of the right atrium, and returned to the initial value when the arm and the transducer were placed back at the right atrial level. Intra-arterial SBP and DBP significantly (P < 0.001) increased as the arm, together with the transducer, were lowered below the right atrial level and returned to the initial value when the arm and the transducer were placed back at the right atrial level. In both directions, each 5 cm change in the arm level was accompanied by a 3-4 mm Hg change in the i.a. BP value. The baseline BP, measured sphygmomanometrically at the contralateral arm, remained constant during the whole duration of the procedure. The changes in the i.a. BP were minimal in the second group of nine subjects in which only the arm but not the transducer was placed at different levels. We conclude that small deviations in arm position above or below the 'gold standard', ie, the fossa cubiti at the right atrial level, will result in largely erroneous BP values. The correct positioning of the arm during BP measurement is therefore mandatory for the diagnosis and follow-up of hypertensive subjects.

Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans.

Experimental data show that ATP-sensitive potassium (KATP) channels not only occur in pancreatic beta cells, but also in the cardiovascular system, where they mediate important cardioprotective mechanisms. Sulphonylurea derivatives can block the cardiovascular KATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular KATP channels in humans. Using venous-occlusion strain-gauge plethysmography, we investigated whether ischaemia-induced reactive hyperaemia is reduced by the sulphonylurea derivative glibenclamide in 12 healthy male non-smoking volunteers. Forearm vasodilator responses to three periods of arterial occlusion (2, 5 and 13 min) during concomitant infusion of placebo into the brachial artery were compared with responses during concomitant intra-arterial infusion of glibenclamide (0.33 microgram.min-1.dl-1). A control study (n = 6) showed that time itself did not change the vasodilator response to ischaemia. Glibenclamide significantly increased minimal vascular resistance (from 2.1 +/- 0.1 to 2.3 +/- 0.2 arbitrary units, Student's t-test: p = 0.01), and reduced mean forearm blood flow (from 37.5 +/- 2.0 to 35.4 +/- 2.0 ml min-1.dl-1 after 13 min occlusion, ANOVA with repeated measures: p = 0.006) and flow debt repayment during the first reperfusion minute (ANOVA with repeated measures: p = 0.04). In contrast, total flow debt repayment was not affected. Infusion of glibenclamide into the brachial artery resulted in local concentrations in the clinically relevant range, whereas the systemic concentration remained too low to elicit hypoglycaemic effects. Our results suggest that therapeutic concentrations of glibenclamide induce a slight but significant reduction in the early and peak vasodilation during reactive hyperaemia.

Interaction of sulphonylurea derivatives with vascular ATP-sensitive potassium channels in humans.

Cardiovascular adenosine-5'-triphosphate-sensitive potassium (KATP) channels have been reported to play an important role in endogenous cardioprotective mechanisms. Sulphonylurea derivatives can inhibit these cardioprotective mechanisms in animal models. We investigated whether therapeutic concentrations of sulphonylurea derivatives can block vascular KATP channels in humans. The forearm vasodilator responses to administration of the specific KATP channel opener diazoxide into the brachial artery of healthy male volunteers were recorded by venous occlusion plethysmography. This procedure was repeated with concomitant intraarterial infusion of:1) the sulphonylurea derivative glibenclamide (0.33 or 3.3 micrograms. min-1. dl-1, both n = 12), 2) the new sulphonylurea derivative glimepiride (2.5 micrograms.min-1. dl-1, n = 12) or 3) placebo (n = 12). The effects of glibenclamide on the vasodilator responses to sodium nitroprusside were also studied (n = 12). Glibenclamide significantly inhibited the diazoxide-induced increase in forearm blood flow ratio (ANOVA with repeated measures: p < 0.01). During the highest diazoxide dose this ratio (mean +/- SEM) was lowered from 892 +/- 165 to 449 +/- 105%, and from 1044 +/- 248 to 663 +/- 114% by low- and high-dose glibenclamide, respectively. In contrast, neither glimepiride nor placebo attenuate diazoxide-induced vasodilation. Furthermore, glibenclamide did not affect nitroprusside-induced vasodilation. We conclude that therapeutic concentrations of the classical sulphonylurea derivative glibenclamide result in significant blockade of vascular KATP channels in humans. The newly developed glimepiride seems to be devoid of these properties.

Effects of tolbutamide on vascular ATP-sensitive potassium channels in humans. Comparison with literature data on glibenclamide and glimepiride.

Sulfonylurea (SU) derivatives exert their hypoglycemic effect by blockade of adenosine-5'-triphosphate-sensitive potassium (KATP) channels in the beta-cell of the pancreas. Interestingly, KATP channels also occur in the cardiovascular system, where they are thought to play an important role in cardioprotective mechanisms against ischemia. We have recently shown that the classical second generation SU-derivative glibenclamide is able to block vascular KATP channels in man, whereas the newly developed second generation derivative glimepiride was devoid of this property. The aim of this study was to determine whether the first generation SU derivative tolbutamide has KATP channel blocking properties in humans. In a group of 12 healthy male non-smoking volunteers, we investigated whether therapeutic concentrations of tolbutamide were able to inhibit the forearm vasodilation in response to the infusion of the KATP channel opening drug diazoxide into the brachial artery. Changes in forearm blood flow were recorded by venous occlusion mercury-in-silastic strain-gauge plethysmography. Diazoxide alone increased the forearm blood flow ratio dose-dependently by ultimately 691 +/- 198%. A second diazoxide infusion in the presence of tolbutamide revealed a comparable vasodilator response with a percentage increase in forearm blood flow ratio of ultimately 542 +/- 111%. This response did not differ from the vasodilator response to diazoxide alone. The present study shows that therapeutic concentrations of tolbutamide are not able to attenuate the vasodilation caused by the KATP channel opener diazoxide in man. When compared with published data on second generation SU derivatives, tolbutamide shows an intermediate position between glibenclamide (with significant blockade of vascular KATP channels) versus glimepiride (with no blockade at all). It remains to be determined whether these acute effects of SU derivatives on pharmacological opening of forearm vascular KATP channels can be extrapolated to the chronic effects of these drugs on ischemia-mediated opening of myocardial KATP channels during treatment of NIDDM patients.

Clinical and biochemical criteria in the detection of renal artery stenosis.

OBJECTIVE: To investigate methods to diagnose renal artery stenosis (RAS) among the general hypertensive population. METHODS: We studied the value of clinical and biochemical characteristics at the outpatient clinic to identify subjects with a renal artery narrowing of more than 50% of the luminal surface among 1047 hypertensive patients. Included in the analysis were: blood pressure, age, sex, body mass index, endogeneous creatinine clearance, smoking and plasma renin activity. RESULTS: Among the 1047 patients, 355 were selected for angiography. In this subgroup 104 patients (29%) had RAS. The subjects with RAS had significantly higher diastolic and systolic blood pressures than did those without stenosis. Forward stepwise logistical regression analysis showed that systolic blood pressure, stimulated plasma renin activity and smoking were the most predictive independent screening variables for the presence of RAS. Yet, none of these characteristics or their combinations were sufficiently sensitive to distinguish reliably between patients with essential hypertension and those with RAS. Sytolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg on automatic (Dinamap) recording as criteria selected a subgroup of patients with a RAS prevalence of 30%. CONCLUSIONS: By using blood pressure screening criteria a subgroup of hypertensive patients with a high prevalence of RAS can be formed in whom further invasive tests for RAS are indicated and efficient.

Cardiovascular effects of sulphonylurea derivatives.

The classical sulphonylurea derivatives like glibenclamide and tolbutamide are widely prescribed in non-insulin dependent diabetes mellitus in order to stimulate insulin secretion. The insulinotropic effect of these agents is based on the closure of adenosine-5'-triphosphate (ATP)-sensitive potassium channels (KATP-channels) in the beta-cells of the pancreas. Interestingly, the cardiovascular system also shares these KATP-channels. The open state probability of these channels is regulated by the intracellular concentration of ATP. During ischaemia, the KATP-channels are thought to open by a fall in the cytosolic ATP concentration. The increase in the extracellular adenosine concentration, and the release of endothelium-derived hyperpolarizing factor (EDHF) during ischaemia may further contribute to the opening of cardiovascular KATP-channels. Sulphonylurea derivatives like glibenclamide and tolbutamide have been reported to block the opening of KATP-channels in several types of tissues including myocardial and vascular smooth muscle cells. Since the opening of KATP-channels is regarded as an endogenous cardioprotective mechanism, the blocking effect of sulphonylurea derivatives in the cardiovascular system may have deleterious effects. Human studies on this issue have just been initiated, and preliminary results point towards a significant interaction between glibenclamide and cardiovascular KATP-channels at clinically relevant concentrations. In this regard, the introduction of more pancreas specific sulphonylurea derivatives like glimepiride, which do not interact with cardiovascular KATP-channels, is a promising development.

Pattern recognition of loss of early systolic peak by Doppler ultrasound has a low sensitivity for the detection of renal artery stenosis.

In a group of 57 hypertensive patients seen in the out-patient department, the authors did a prospective study to the value of pattern recognition of changes in early systolic peak by Doppler ultrasound (DU) in the examination of renal arteries, as compared with intra-arterial digital subtraction angiography. In five patients (8.7%) DU resulted in technical failure, in one because of the inability to hold breath long enough, in one because the Doppler signals from one part of the kidney were unclear and in three because overlying adipose tissue hindered the examination. Among the remaining 52 patients, 13 had unilateral and six bilateral stenoses greater than 50% of the luminal surface on angiography. By DU 10 patients with a stenosis were identified, one of which was a false positive result. Of the remaining nine, six patients had a unilateral stenosis and three a bilateral stenosis that was identified as unilateral by ultrasound. Therefore, none of the bilateral stenosis was identified as such by DU. Thus, for the detection of renal artery stenoses greater than 50% visual waveform analysis of DU signals has a sensitivity of 47% and a specificity of 97%. The conclusion is therefore that the DU procedure employed in this study has a limited value in the examination of the renal arteries of hypertensive patients with the aim to detect renal arterial stenosis.

Effect of long-term angiotensin-converting enzyme inhibition on endothelial function in patients with the insulin-resistance syndrome.

Cardiovascular risk factors such as hypertension, diabetes, and dyslipemia are associated with an impaired endothelium-dependent vasodilation. In patients with type 2 diabetes mellitus, these risk factors are frequently clustered. We investigated whether long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril can improve endothelium-dependent vasodilation in this particular group of patients. We selected 10 patients with type 2 diabetes and hypertension (age 59.4 +/- 3.2 years, body mass-index 29.7 +/- 1.5 kg.m-2, blood pressure 169 +/- 6/92 +/- 1 mm Hg, total cholesterol 6.6 +/- 0.3 mM). Using venous occlusion plethysmography, we recorded the increases in forearm blood flow (FBF) in response to three vasodilator stimuli: (a) 5 min of forearm ischemia, (b) infusion of the endothelium-dependent vasodilator methacholine (Mch) into the brachial artery (0.03, 0.3, and 1.0 micrograms/min/100 ml), and (c) intraarterial infusion of the endothelium-independent vasodilator sodium nitroprusside (SNP 0.06, 0.2, 0.6 microgram/min/100 ml). This procedure was repeated after 6 months of treatment with perindopril 4-8 mg/day. Forearm vascular resistance (FVR) was calculated by the quotient of the mean arterial pressure (MAP) and the FBF. Perindopril reduced blood pressure (BP) by 19/10 mm Hg (p < 0.05) and increased baseline FVR, but improved neither the maximal percentage decrease in vascular resistance induced by Mch (from -80 +/- 2 to -82 +/- 2%) nor that induced by SNP (from -73 +/- 3 to -72 +/- 3%). Perindopril decreased the FVR reached after the ischemic stimulus from 6.5 +/- 1.2 to 4.8 +/- 0.6 U (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)