ObjectivesBecause existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ.MethodsBased on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis.ResultsEFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1–4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5–10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765–0.920 (SFQ-total), 0.766–0.877 (SFQ-s), and 0.628–0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity.DiscussionThe SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.

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Aims Most cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour‐intensive and carries a risk of hypoglycaemia. We hypothesized that preoperative administration of the glucagon‐like peptide‐1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery. Materials and methods In this randomized, blinded, placebo‐controlled, parallel‐group, balanced (1:1), multicentre randomized, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomized to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia or matching placebo. Blood glucose was measured hourly and controlled using an insulin‐bolus algorithm. The primary outcome was insulin administration for blood glucose >8.0 mmol/L in the operating theatre. Research pharmacists used centralized, stratified, variable‐block, randomization software. Patients, care providers and study personnel were blinded to treatment allocation. Results Between June 2017 and August 2018, 278 patients were randomized to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention‐to‐treat analyses (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group, 55 (43%) patients required additional insulin compared with 80 (61%) in the placebo group and absolute difference 18% (95% confidence interval 5.9–30.0, P = 0.003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality or postoperative complications. Conclusions Preoperative liraglutide, compared with placebo, reduces insulin requirements while improving perioperative glycaemic control during cardiac surgery.

Editor-Guedel used ocular signs as part of his classic description of the four stages of ether anaesthesia in 1937. These were deemed to be relevant clinical tools when ether, cyclopropane, and chloroform were in use, but with newer drugs and advanced monitoring, the eye signs gradually faded into obscurity.We report a case of off-label use of dexmedetomidine with bupivacaine for epidural anaesthesia that led to deep sedation and bilateral miosis.A 62-yr-old female patient, ASA I, was to undergo vaginal hysterectomy. Under strict asepsis, an 18 G epidural catheter was placed in the L3 -4 space. A test dose of 3 ml of 2% lidocaine with epinephrine 5 mg ml 21 was given after which 12 ml of 0.5% bupivacaine with dexmedetomidine 1 mg kg 21 was administered through the epidural catheter. After an initial increase to 190/110 mm Hg, arterial pressure decreased to 90/40 mm Hg and heart rate to 46 beats min 21 over the next 5 min. The patient was breathing normally with 99% oxygen saturation but was deeply sedated and was not responding even to painful stimulus (Ramsay score 6). Rapid infusion of i.v. fluids was started and i.v. atropine 0.6 mg was given. Oxygen was delivered by a facemask and a quick re-check was done to exclude any medication error. The pupils were pinpoint in ambient light and a possibility of pontine haemorrhage was also considered. However, the patient started to stabilize gradually and the sedation score improved to 3 after 30 min. The sensory block was adequate and the surgery could be performed as planned. The rest of the perioperative period was uneventful without any neurological sequelae.While a plethora of information exists about the clinical effects of dexmedetomidine in the anaesthesia journals, little has been said about its effects on the pupils. We examined the current medical literature for its mechanism of action and the effect on reflex pupillary reaction in humans. 1 -4 The regulation of sedation, autonomic function, and pupillary reaction are all inter-related and controlled centrally at the locus coeruleus (LC) due to stimulation of presynaptic a 2Aadrenergic receptors by dexmedetomidine. The LC is the largest group of noradrenergic neurones in the central nervous system and gives rise to fibres innervating most structures of the neuraxis. Any pharmacological alteration to this neuronal circuitry would affect the activity at the LC and clinically result in changes in the level of sedation, heart rate, arterial pressure, and pupil size.There is a biphasic response with dexmedetomidine, with an initial transient sympathomimetic action (peripheral postsynaptic action leading to hypertension) followed by a persistent sympatholytic effect (hypotension and bradycardia). The central sympatholytic action also causes a reduction in pupil diameter due to attenuation of the activity of the coeruleo-spinal pathway and reduction in noradrenergically mediated inhibition of the Edinger-Westphal nucleus. This action is known to predominate in comparison with the peripheral post-synaptic a 2 -adr...

1 We evaluated responses of peripheral resistance arterial smooth muscle to a 1 -adrenoceptor stimulation in a rat model of heart failure in relation to neurohumoral changes, wall structure, receptor density and cellular calcium handling. 2 Plasma samples and third order mesenteric artery side-branches were obtained from Wistar rats after induction of left ventricular infarction (MI) or sham surgery. Vessels were denuded of endothelium, sympathectomized, depleted of neuropeptides, and mounted in a myograph for recording of isometric force development in response to calcium, agonist and high potassium. Also, the morphology of these preparations was determined. Separate vessel segments were used in radioligand binding assays with [3 At 1 week after MI, circulating plasma levels of adrenaline, angiotensin II, atrial natriuretic factor (ANF) and vasopressin were signi®cantly elevated. At 5 weeks only a signi®cant elevation of ANF persisted. 4 At 5 weeks after MI, the structure of the vessels and responsiveness to high potassium or Bay K 8466 (10 76 mol l 71 ) were not modi®ed. Yet, at this stage, sensitivity to phenylephrine was increased (pD 2 : 6.24+0.04 vs 5.98+0.04 for controls) while maximal contractile responses to phenylephrine in the presence of 2.5 mmol l 71 calcium (2.26+0.28 vs 3.53+0.34 N m 71) and the sensitivity to calcium in the presence of phenylephrine (pD 2 : 2.81+0.22 vs 3.74+0.16) were reduced. Responses to the agonist in calcium-free solution and the calcium sensitivity in the presence of 125 mmol l 71 potassium or of phorbol myristate acetate (PMA, 10 76 mol l 71 ) were not altered. 5 At 5 weeks after MI, the density of prazosin binding sites was not reduced (4.04+1.40 vs 2.29+0.21 fmol mg 71 DNA in controls). 6 In conclusion, myocardial infarction leads in the rat to a reduction of contractile responses of mesenteric resistance arterial smooth muscle to a 1 -adrenoceptor stimulation. This seems to involve impaired agonist-stimulated calcium in¯ux.

Collagen degradation is suggested to be responsible for long-term contractile dysfunction in different cardiomyopathies, but the effects of acute and specific collagen type I removal (main type in the heart muscle) on tension have not been studied. We determined the diastolic and developed tension length relations in isometric contracting perfused rat papillary muscles (perfusion pressure 60 cmH(2)O) before and after acute and specific removal of small collagen struts with the use of purified collagenase type I. At 95% of the maximal length (95%L(max)), diastolic tension increased 20.4 +/- 8.1% (P < 0.05, n = 6) and developed tension increased 15.0 +/- 6.7% after collagenase treatment compared with time controls. Treatment increased the diastolic muscle diameter by 7.1 +/- 3.4% at 95%L(max), whereas the change in diameter due to contraction was not changed. Diastolic coronary flow and normalized coronary arterial flow impediment did not change after collagenase treatment. Electron microscopy revealed that the number of small collagen struts, interconnecting myocytes, and capillaries was reduced to approximately 32% after treatment. We conclude that removal of the small collagen struts by acute and specific collagen type I degradation increases diastolic and developed tension in perfused papillary muscle. We suggest that diastolic tension is increased due to edema, whereas developed tension is increased because the removal of the struts poses a lower lateral load on the cardiac myocytes, allowing more myocyte thickening.

Coronary arterial inflow is impeded and venous outflow is increased as a result of the decrease in coronary vascular volume due to cardiac contraction. We evaluated whether cardiac contraction is influenced by interfering with the changes of the coronary vascular volume over the heart cycle. Length-tension relationships were determined in Tyrode-perfused rat papillary muscle and when coronary vascular volume changes were partly inhibited by filling it with congealed gelatin or perfusing it with a high viscosity dextran buffer. Also, myocyte thickening during contraction was reduced by placing a silicon tube around the muscle. Increasing perfusion pressure from 8 to 80 cmH2O, increased developed tension by approximately 40%. When compared with the low perfusion state, developed tension of the gelatin-filled vasculature was reduced to 43 +/- 6% at the muscle length where the muscle generates the largest developed tension (n = 5, means +/- SE). Dextran reduced developed tension to 73 +/- 6% (n = 6). The silicon tube, in low perfusion state, reduced the developed tension to 83 +/- 7% (n = 4) of control. Time-control and oxygen-lowering experiments show that the findings are based on mechanical effects. Thus interventions to prevent myocyte thickening reduce developed tension. We hypothesize that when myocyte thickening is prevented, intracellular pressure increases and counteracts the force produced by the contractile apparatus. We conclude that emptying of the coronary vasculature serves a physiological purpose by facilitating cardiomyocyte thickening thereby augmenting force development.

IntroductionPerioperative hyperglycaemia is common during cardiac surgery and associated with postoperative complications. Although intensive insulin therapy for glycaemic control can reduce complications, it carries the risk of hypoglycaemia. GLP-1 therapy has the potential to lower glucose without causing hypoglycaemia. We hypothesise that preoperative liraglutide (a synthetic GLP-1 analogue) will reduce the number of patients requiring insulin to achieve glucose values<8 mmol l-1 in the intraoperative period.Methods and analysisWe designed a multi-centre randomised parallel placebo-controlled trial and aim to include 274 patients undergoing cardiac surgery, aged 18–80 years, with or without diabetes mellitus. Patients will receive 0.6 mg liraglutide or placebo on the evening before, and 1.2 mg liraglutide or placebo just prior to surgery. Blood glucose is measured hourly and controlled with an insulin bolus algorithm, with a glycaemic target between 4–8 mmol l−1. The primary outcome is the percentage of patients requiring insulin intraoperatively.Ethics and disseminationThis study protocol has been approved by the medical ethics committee of the Academic Medical Centre (AMC) in Amsterdam and by the Dutch competent authority. The study is investigator-initiated and the AMC, as sponsor, will remain owner of all data and have all publication rights. Results will be submitted for publication in a peer-reviewed international medical journal.Trial registration numberNTR6323; Pre-results.