Cardiac surgery with cardiopulmonary bypass (CPB) is commonly perceived as a risk factor for decline in renal function, especially in patients with preoperative renal dysfunction. There are few data on the effects of CPB on renal function in patients with mild preoperative renal dysfunction. The purpose of this study was to evaluate renal function in patients with pre-existing mild renal dysfunction undergoing cardiac surgery with CPB.
In a multicentre study cohort we measured prospectively the glomerular filtration rate (GFR) by radioactive markers both before operation and on the 7th postoperative day in cardiac surgical patients with preoperative serum creatinine >120 µmol l–1 (n=56). In a subgroup of patients (n=14) in addition to the GFR, the effective renal plasma flow (ERPF) and the filtration fraction (FF) were measured.
While preoperative GFR [77.9 (25.5) ml min–1] increased to 84.4 (23.7) ml min–1 (P=0.005) 1 week after surgery, ERPF did not change [295.8 (75.2) ml min–1 and 295.9 (75.9) ml min–1, respectively; P=0.8]. In accordance, the FF increased from 0.27 (0.05) (before operation) to 0.30 (0.04) (Day 7, P=0.01).
Our results oppose the view that cardiac surgery with CPB adversely affects renal function in patients with preoperative mild renal dysfunction and an uncomplicated clinical course.
S-(+)-ketamine anaesthesia carries potential benefits for the cardiovascularly compromised patient. However, the use of S-(+)-ketamine in ischaemic coronary artery disease is controversial. In a prospective, randomized, clinical trial, we have investigated whether an S-(+)-ketamine-based anaesthetic protocol leads to increased cardiac troponin T levels (cTnT) after coronary artery bypass grafting (CABG).
Two hundred and nine patients undergoing elective CABG were randomized to receive either i.v. anaesthesia with sufentanil–midazolam–propofol (SMP; n=108) or S-(+)-ketamine–midazolam–propofol (KMP; n=101). Haemodynamic variables were maintained within the normal range. Invasive haemodynamic monitoring was performed using a pulmonary artery catheter. Plasma cTnT levels were sampled before induction and 1, 6, and 24 h after aortic unclamping. Cardiovascular adverse events, such as electrocardiographic signs of ischaemia, perioperative myocardial infarction, and death, were recorded.
Patient characteristics, cardiac profile, intraoperative management, and the incidence of cardiovascular adverse events were comparable between the groups. Plasma cTnT levels increased after operation in both groups. cTnT levels were significantly lower in the KMP group 6 h after aortic unclamping compared with the SMP group (P=0.004), but did not differ 24 h after aortic unclamping [median (range): SMP 0.4 (0.01–3.9) vs KMP 0.4 (0.07–6.6) µg litre–1, P=0.338].
S-(+)-ketamine does not accentuate postoperative cTNT rises in haemodynamically stable elective CABG patients.
During general anaesthesia, the most prominent change in heart rate variability (HRV) is a decrease in the magnitude of heart rate (HR) oscillation in the high- and low-frequency ranges. In children receiving sevoflurane or desflurane, we observed a significant increase in HR non-stationarity, that is, a significant change of mean HR over time. The aim of our study was to describe this increased non-stationarity and compare it with the decrease in the magnitude of HR oscillation.
Sixty children received sevoflurane (n=30) or desflurane anaesthesia (n=30). The magnitude of HR oscillation and non-stationarity during pre-anaesthesia and anaesthesia were measured by spectral and Hurst analyses using structure function, respectively.
Low- and high-frequency powers decreased significantly and the very-short-term (2≤≤8 s, H) and short-term Hurst exponent (8≤≤45 s, Hβ) increased significantly during the anaesthetic period compared with the pre-anaesthetic period, regardless of the anaesthetic agent [sevoflurane: mean (
During sevoflurane and desflurane anaesthesia in children, there is a significant increase in very-short-term and short-term HR non-stationarity. Furthermore, the greater short-term non-stationarity differentiates better between the pre-anaesthesia and anaesthesia than the decreased magnitude of HR oscillation in the high- and low-frequency ranges.
Nitrous oxide (N2O) inhibits methionine synthetase resulting in elevated plasma homocysteine (Hcy) concentration after surgery. In epidemiological studies, hyperhomocysteinaemia is associated with increased risk of cardiovascular disease and dementia.
Blood samples were obtained to measure plasma folate and Hcy concentrations from two centres participating in a multicentre randomized trial investigating the effects of N2O on the outcome after major surgery. The effect of N2O and duration of anaesthesia on plasma Hcy, and the relationship between hyperhomocysteinaemia and outcomes were assessed.
We enrolled 394 patients. The N2O Group had an increase in plasma Hcy concentration after surgery when compared with the N2O-free Group: 11.1 (3.8) vs 8.5 (4.0) µmol litre–1, P<0.0005. Postoperative hyperhomocysteinaemia was associated with an increased risk of major complications: risk ratio (RR) 2.8 (95% CI: 1.4–5.4), P=0.002 and cardiovascular events, RR 5.1 (95% CI: 3.1–8.5), P<0.0005. There was a significant association between duration of anaesthesia and the relative change in plasma Hcy concentration, particularly in the N2O Group: r=0.42, P<0.001.
N2O increases plasma Hcy concentration; this effect is greater with a longer duration of anaesthesia. Hyperhomocysteinaemia is a risk factor for major postoperative complications. N2O-induced increases in plasma Hcy concentration may be a cause of postoperative cardiovascular morbidity.
Xenon has been proved to be safe and efficacious for general anaesthesia in numerous trials. In addition, experimental studies demonstrate that xenon inhibits the 5-hydroxytryptamine type 3 (5-HT3) receptor. As 5-HT3 receptor antagonists are known to decrease postoperative nausea and vomiting (PONV) to an extent comparable with a propofol-based total i.v. technique, we tested the hypothesis that general anaesthesia with xenon would result in a reduced incidence of PONV similar to that observed with propofol-based anaesthesia.
After obtaining approval from the local ethics committee and written informed consent, 142 patients were randomized to receive xenon anaesthesia or propofol-based total i.v. anaesthesia (TIVA), both supplemented with remifentanil. The incidence of postoperative nausea and emetic episodes was recorded in the post-anaesthesia care unit and on the ward more than 24 h after anaesthesia.
A total of 142 patients were equally distributed between the xenon and TIVA groups. Anaesthesia was maintained with mean (
Despite knowing the 5-HT3 antagonistic properties of xenon, its use is associated with a higher incidence of nausea and emetic episodes compared with TIVA with propofol.
Blood loss and uncontrollable bleeding are major factors affecting survival in trauma patients. Because treatment with antifibrinolytic drugs may be effective, early detection of hyperfibrinolysis with rotation thrombelastography (ROTEM®) may be beneficial.
Eighty-seven trauma patients were included in this prospective observational study. Blood samples were collected at admission. After in vitro activation with tissue factor (EXTEM) and inhibition with aprotinin (APTEM), ROTEM® parameters including maximal clot firmness (MCF) and clot lysis index at 30 min (CLI30) were determined. Hyperfibrinolysis was defined as a euglobulin lysis time (ELT) <90 min. Threshold for ROTEM® parameters were determined with receiver-operating characteristic curves (ROC) analysis according to the ELT results.
ELT was determined in a subgroup of 23 patients. In this group of patients, ROC analysis showed that for a threshold of 18 mm (MCF-EXTEM), 71% (CLI30) and 7% (increase of MCF-APTEM), sensitivity was, respectively, 100%, 75%, and 80% with a specificity of 100%. With the application of these thresholds to the whole trauma cohort, ROTEM® analysis detected hyperfibrinolysis in five patients [6%, 95% confidence interval (CI): 2–13%]. As expected, patients with hyperfibrinolysis were more severely injured (median Injury Severity Score: 75 vs 20, P<0.05), had greater coagulation abnormalities [international normalized ratio (INR): 8.2 vs 1.3, P<0.05; fibrinogen: 0.0 vs 2.2 g litre–1, P<0.05], and a higher mortality rate (100%, CI: 48–100% vs 11% CI: 5–20%, P<0.05).
ROTEM® provided rapid and accurate detection of hyperfibrinolysis in severely injured trauma patients.
Corticosteroids interact with neuromuscular blocking agents. However, experimental data are contradictory: enhancement and attenuation of the neuromuscular block has been observed. This study tested the influence of long-term medication with prednisolone on atracurium-induced neuromuscular block.
Sixty patients with chronic inflammatory bowel disease undergoing elective abdominal surgery were investigated. Thirty patients received a long-term medication with prednisolone (Group A) and 30 were without corticoid medication (Group B). Additionally, another 30 patients without inflammatory bowel disease and without corticoid medication served as control (Group C). The following parameters of an atracurium-induced neuromuscular block (0.25 mg kg–1) were measured: onset time, maximum block, recovery to 25% first twitch height, recovery index (time from 25% until 75% recovery of first twitch), duration to recovery to a train-of-four (TOF) rate of 0.7 and 0.9.
The groups did not differ with regard to onset time, maximum block, and recovery index. The duration to 25% twitch height was significantly lower in Group A [18.1 (0–30.7) min] compared with Group B [23.5 (0–36.7) min; P<0.05]. Duration to a TOF rate of 0.7 and 0.9, respectively, were significantly reduced in Group A [36.1 (7.9) and 40.9 (9.0 min)] compared with Group B [47.9 (7.6) and 53.4 (9.2) min; P<0.001].
Long-term medication with prednisolone resulted in a shorter duration of an atracurium-induced neuromuscular block in patients with Crohn's disease or ulcerative colitis. The presence of the inflammatory bowel disease did not influence the time course of the neuromuscular block.
Septic shock includes blood vessel dilatation and activation of innate immunity, which in turn causes release of antimicrobial peptides such as LL-37. It has been shown that LL-37 can attract leucocytes via the lipoxin A4 receptor (ALX, FPRL1). ALX is also present in vascular endothelial cells. To explore possible ways of pharmacological intervention in septic shock, we investigated if LL-37 can affect vascular tone.
Human omental arteries and veins were obtained during abdominal surgery, and circular smooth muscle activity was studied in organ baths. Gene expression was studied using reverse transcriptase–polymerase chain reaction.
LL-37, at micromolar concentrations, induced a concentration- and endothelium-dependent relaxation in vein but not in artery segments precontracted by endothelin-1. The relaxation was profoundly reduced by potassium chloride (30 mM) to inhibit endothelium-derived hyperpolarizing factor (EDHF), whereas it was less affected by the NOS inhibitor,
We demonstrate, for the first time, that the human antimicrobial peptide, LL-37, induces endothelium-dependent relaxation in human omental veins mediated via an effect on endothelial ALX. The relaxation involves the release of nitric oxide and EDHF but not prostanoids. LL-37 released from white blood cells could contribute to blood vessel dilatation during sepsis and treatment with ALX antagonists might be successful.
The systemic inflammatory response to infection (sepsis) involves widespread organ dysfunction, including changes in immune modulation, cardiovascular derangements, and neural activation. Two neuropeptide/receptor systems, nociceptin/orphanin FQ (N/OFQ) which acts at the non-classical opioid receptor NOP and urotensin-II (U-II) which acts at the urotensin receptor (UT), have been implicated in neural, immune, and cardiovascular system function. In this study, we make measurements of these peptides in critically ill patients.
Plasma samples from 21 critically ill patients with sepsis were collected over four consecutive days. Plasma N/OFQ and U-II concentrations were determined by radioimmunoassay and compared with biochemical and clinical markers of illness severity, including serum creatinine, bilirubin, platelet and white cell counts, admission APACHE II and serial SOFA scores.
Median (inter-quartile range) admission plasma N/OFQ concentrations in sepsis were higher in patients who died within 30 days (n=4) compared with survivors (n=17); 3.0 (2.5–5.0) vs 1.0 (1.0–2.5) pg ml–1 (P=0.028). Plasma N/OFQ concentrations were increased in a subgroup of five patients who had undergone major gastrointestinal surgery. There were no significant changes in plasma U-II concentrations. There were no correlations between plasma U-II and N/OFQ concentrations and markers of illness severity and organ system dysfunction.
Plasma N/OFQ concentrations were increased in critically ill patients with sepsis who had undergone major gastrointestinal surgery and in patients who subsequently died. Further work is required to clarify the significance of plasma N/OFQ concentrations in sepsis.
Activated protein C (APC) therapy reduces mortality in high-risk patients with severe sepsis. The effects of APC on inflammatory responses have also been reported. Neutrophils are key cells involved in early host defence mechanisms in sepsis. We hypothesized that APC may have effects on neutrophil function.
Neutrophils were isolated from 10 healthy volunteers and incubated in the presence of lipopolysaccharide (LPS) with and without a range of therapeutically relevant concentrations of recombinant human APC. Respiratory burst activity was determined using flow-activated cell sorting (FACS) analysis. Apoptosis was determined using Annexin-V staining and FACS analysis. Cytokine bead array was used to simultaneously measure three key cytokines in culture supernatants: interleukin (IL)-1β, -6, and -8. For chemotaxis, neutrophil migration through a 5 µm membrane was measured in response to formyl–methyl–leucine–phenylalanine (FMLP) or IL-8 in the presence and absence of APC.
Exposure to LPS resulted in significant increases in respiratory burst activity, IL-1β, -6, and -8 expression (all P<0.0001) and decreased the number of apoptotic cells (P<0.0001). The APC exposure resulted in a significant release of IL-6 (P=0.04) without affecting other cytokines. Respiratory burst and apoptosis were also unaffected by APC. Neutrophil chemotaxis in response to either FMLP or IL-8 was reduced by APC (P=0.005 and 0.007, respectively).
This pilot study showed that APC treatment of human neutrophils results in a decreased IL-6 expression and chemotaxis, without affecting other cytokines, apoptosis, or respiratory burst activity.
In the UK demand for organ transplantation continues to outstrip supply and one strategy aimed at reversing this trend is the introduction of non-heart beating donor (NHBD) schemes. In this paper we describe our experience after the introduction of the NHBD scheme at a regional neuroscience intensive care unit (ICU) that also provides general intensive care.
We describe the steps taken to establish the scheme and present our results from the time of its implementation in July 2002 until March 2007.
Of the 100 patients whom we referred to the transplant co-ordinators, 71 were identified as potential NHBDs and of these 29 went on to become actual donors (conversion rate of 40.8%). Fifty-six kidneys were retrieved and 53 successfully transplanted. In addition, two livers were retrieved but subsequently found to be unsuitable for transplantation, while eight pancreas were retrieved and used for islet cell research. The serum creatinine at 1 yr demonstrates that there is no significant difference between transplanted kidney function from NHBDs and heart-beating donors (HBDs).
We believe that by establishing the NHBD organ donation scheme we are able to fulfil the wishes of more patients who have indicated that they would like to donate their organs while increasing the availability of solid organs for transplantation. With careful preparation, audit, and communication our experience demonstrates that the NHBD scheme can be successfully introduced in an ICU and expanded to other ICUs in a region.
Lornoxicam like other non-steroidal anti-inflammatory drugs (NSAIDs) is widely used for postoperative pain therapy. Evaluation of the effect of lornoxicam on cerebral processing of surgical pain was thus the aim of the present functional magnetic resonance imaging (fMRI) study.
An fMRI-compatible pain model that mimics surgical pain was used to induce pain rated 4–5 on a visual analogue scale (VAS) at the anterior margin of the right tibia in volunteers (n=22) after i.v. administration of saline (n=11) or lornoxicam (0.1 mg kg–1) (n=11).
Lornoxicam, which significantly reduced pain sensation [VAS: mean (
As compared with saline, lornoxicam typically suppressed pain-induced brain activation in all regions except the hippocampus. Furthermore, de novo activation was found in the contralateral, superior parietal lobe (BA 7).
Multimodal pain management has been suggested to improve postoperative analgesia. In this study, we evaluated the quality of analgesia in women undergoing day-case gynaecological laparoscopic surgery, after premedication with pregabalin 75 mg (P75) or 150 mg (P150), compared with diazepam 5 mg (D5). All patients were given ibuprofen 800 mg orally.
Altogether 90 consenting women were anaesthetized in a standardized fashion. Postoperative analgesia was provided by ibuprofen 800 mg twice a day with fentanyl i.v. on request in the recovery room (RR), and combination tablets with acetaminophen and codeine after the RR. The visual analogue scale (VAS) scores for pain and side-effects and the amounts of postoperative analgesics were recorded for 24 h after surgery. The areas under the curves (AUC) were calculated for the VAS scores for pain at rest, pain in motion, and pain at cough 1–8 and 1–24 h after surgery.
The median AUC values for VAS scores for pain at rest (P=0.048) and in motion (P=0.046) 1–8 h after surgery were lower in the P150 group than that in the D5 group. The amounts of rescue analgesics or the degree of drowsiness did not differ in the three study groups.
Analgesia was better after premedication with pregabalin 150 mg than after diazepam 5 mg, both with ibuprofen 800 mg, during the early recovery after day-case gynaecological laparoscopic surgery. Pregabalin 150 mg did not reduce the amount of postoperative analgesics required.
We have previously reported that landiolol, an ultra-short-acting β1-adrenoceptor antagonist, does not alter the anaesthetic effects of isoflurane. Here, we investigated the influence of propranolol on the electroencephalographic (EEG) effects and minimum alveolar concentration (MAC) of isoflurane.
Fourteen swine [25.0 (
Propranolol shifted the concentration–effect relationship to the left and decreased the effect–site concentration that produced 50% of the maximal effect from 1.30 (0.18) to 1.13 (0.17)%. Propranolol also decreased isoflurane MAC from 1.91 (0.35) to 1.54 (0.32)%.
Propranolol alters both the hypnotic and anti-nociceptive effects of isoflurane. In contrast to landiolol, lipophilic β-adrenoceptor antagonists may increase the potency of inhalational anaesthetics.
Spinal catheters, because of their smaller diameter, have lower tensile strength than epidural catheters. This study was designed to measure the withdrawal forces needed to remove lumbar spinal catheters and to determine whether patient position affects withdrawal forces.
Eighty-two patients with a 24-gauge spinal catheter placed midline at the lumbar L3/4 or L4/5 level were randomly assigned to catheter removal either in flexed lateral or sitting position. Withdrawal forces were measured using a tension spring balance.
Mean withdrawal force was 0.91 N (95% CI: 0.73, 1.09) with extremes up to 5 N. Withdrawal force in the flexed lateral position was 1.04 N (95% CI: 0.73, 1.34) or in the sitting position was 0.78 N (95% CI: 0.59, 0.97). The 95% CI for the difference of the means was –0.62 N, 0.10 N. Thus, the absolute mean difference between the positions can be assumed to be smaller than 0.62 N. Neither the length of the spinal catheter under the skin or in the subarachnoid space, nor BMI influenced withdrawal force.
Withdrawal force of spinal catheters is not influenced by body position during catheter removal, length of catheter under skin, or BMI.
Two hundred anaesthetists underwent airway endoscopy and attempted awake fibreoptic intubation (FOI) on a training course. Complications were recorded and each subject's response to the procedure was assessed.
Topical airway local anaesthesia was produced with up to 9 mg kg–1 of lidocaine, sedation was not used. Complications during and after the procedure were noted. Later, the subjects completed an anonymous questionnaire about anxiety, pain, coughing, and side-effects of lidocaine.
More than 1300 endoscopies were performed, 180 delegates were intubated, 175 by the nasal route and five orally. Intubation was abandoned in 20 (10%) subjects. Nasal bleeding occurred in 20 (10%) subjects. Symptoms that could be attributed to lidocaine were reported by 71 (36%) subjects. Afterwards, two (1%) subjects experienced rigors and one developed a lower respiratory tract infection.
Nasendoscopy and FOI under local anaesthesia are associated with complications, notably those of infection and airway trauma. Side-effects potentially attributable to lidocaine administration were commonly reported.
The results of two European multi-centre trials on xenon anaesthesia led to the hypothesis that a xenon-based anaesthetic would keep left ventricular (LV) and circulatory function more stable than a propofol-based anaesthetic, in patients with coronary artery disease (CAD).
In a prospective, randomized design, 40 patients of ASA classes III and IV with known CAD were anaesthetized for elective non-cardiac surgery with either xenon (n=20) or propofol (n=20), each combined with remifentanil. Target criteria were intraoperative LV function as evaluated by transoesophageal echocardiography (TOE: Tei index, circumferential fibre shortening), arterial pressure, and heart rate (HR).
Mean arterial pressure was decreased with propofol but was stable at pre-anaesthetic level with xenon (P<0.02) and HR was lower with xenon (P<0.01). The Tei index (also known as myocardial performance index) improved from 0.53 (0.14) to 0.45 (0.10) after 1 h with xenon and changed from 0.50 (0.14) to 0.55 (0.20) with propofol anaesthesia [means (
Xenon anaesthesia provided a higher arterial pressure level than propofol, with no signs of cardiovascular compromise, in patients with CAD. Echocardiographic indices showed better LV function with xenon.
The aim of this study was to investigate the effects of procalcitonin on the lipopolysaccharide (LPS)-induced changes in human leucocytes and porcine isolated coronary artery.
Using flow cytometry, changes in forward scatter and intracellular calcium in human neutrophils and monocytes were determined after exposure to procalcitonin, calcitonin gene-related peptide (CGRP), LPS, and the known chemoattractants formylated methionine-leucine-phenylalanine (fMLP) and interleukin-8 (IL-8). In porcine isolated coronary artery, the effects of procalcitonin were evaluated using the contractile function change and the release of TNF.
In human neutrophils and monocytes, procalcitonin (100 nM), but not CGRP, increased forward scatter and the expression of surface markers (CD16 and CD14, respectively) in a similar manner to 10 µg ml–1 LPS. Procalcitonin, but not CGRP, also increased the proportion of cells exhibiting an increase in intracellular calcium ions similar to that produced by fMLP and IL-8. Acute exposure of the coronary artery to procalcitonin produced a small, endothelium-independent relaxation (approximately 15% of constrictor tone), but failed to modify subsequent relaxations to CGRP. After 16 h exposure, procalcitonin (100 nM) increased TNF release from the coronary artery equivalent to 70% of that produced by LPS, but did not modify the inhibitory effect of LPS (100 µg ml–1) on contractile responses.
Procalcitonin has a proinflammatory effect on human leucocytes and porcine coronary artery, but it is not capable of modulating LPS-induced changes in vascular responsiveness in vitro.
Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated.
Adult surgical patients (ASA class I–III) were randomized to sugammadex 2.0 mg kg–1 for reversal of block induced by rocuronium 0.6 mg kg–1, or neostigmine 50 µg kg–1 for reversal of block induced by cisatracurium 0.15 mg kg–1. Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch® SX). Sugammadex or neostigmine was administered at reappearance of T2. The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9.
Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine (geometric mean=1.9 vs 9.0 min, P<0.0001). Reversal of block was sustained in all patients. There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety, except for similar elevations in urinary N-acetyl glucosaminidase in both groups.
Sugammadex 2.0 mg kg–1 administered at reappearance of T2 was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.
An efficacious, reliable, and non-invasive route of administration for midazolam, a drug used for sedation and pre-anaesthetic medication, would have obvious advantages. This study compares two potential methods of administering midazolam by the nasal and nebulized routes.
Midazolam (0.2 mg kg–1) was given by both nebulizer and nasally by liquid instillation to 10 healthy volunteers in a randomized, double-blind crossover study. Plasma concentrations of midazolam, Ramsay sedation scores, visual analogue scores, critical flicker fusion frequency, and parameters of cardiovascular and respiratory function were measured over 60 min and summarized using ‘area under the curve’.
Nasal instillation caused more sedation than nebulized administration. This was demonstrated by higher Ramsay sedation scores (P=0.005), lower visual analogue scores (P<0.001), and lower critical flicker fusion frequency (P<0.02). Nasal instillation was associated with higher plasma concentrations of midazolam (P<0.001). Unpleasant symptoms were recorded by six volunteers in the intranasal and one in the nebulized group (P=0.06).
There was some evidence that midazolam caused less discomfort when given by nebulizer compared with intranasally. Comparative bioavailability of midazolam, estimated by the ratio (nebulized:nasal) of area under the 60 min plasma concentration curve, was 1:2.9. A higher dose may need to be administered for adequate pre-anaesthetic medication when midazolam is given by nebulizer.
Measuring patient satisfaction after anaesthesia care is complex. The exis