Anaesthesia and Intensive Care

Levosimendan is emerging as a novel cardioprotective inotrope. Levosimendan augments myocardial contractility by sensitising contractile myofilaments to calcium without increasing myosin adenosine triphosphatase activity or oxygen consumption. Levosimendan activates cellular adenosine triphosphate-dependent potassium channels, a mechanism which is postulated to protect cells from ischaemia in a manner similar to ischaemic preconditioning. Levosimendan may therefore protect the ischaemic myocardium during ischaemia-reperfusion as well as improve the contractile function of the heart. Adenosine triphosphate-dependent potassium channel activation by levosimendan may also be protective in other tissues, such as coronary vascular endothelium, kidney and brain. Clinical trials in patients with decompensated heart failure and myocardial ischaemia show levosimendan to improve haemodynamic performance and potentially improve survival. This paper reviews the known pharmacology of levosimendan, the clinical experience with the drug to date and the potential use of levosimendan as a cardioprotective agent during surgery.

Pulsed radiofrequency is a growingly popular pain treatment modality. However, its clinical efficacy remains controversial. In this review, the available literature on pulsed radiofrequency is critically analysed to determine its clinical efficacy. Our search of the literature for pulsed radiofrequency yielded 341 citations; after reviewing the abstracts we found 51 relevant articles. There were 4 review articles: 44 articles pertained to the application of pulsed radiofrequency by an electrode placed in the vicinity of a neural structure. Of these only two were randomised controlled trials. Of the remaining 42 articles, one was a non-randomised controlled trial, three were prospective uncontrolled trials: there were six retrospective studies, 11 case reports, eight laboratory studies, two position papers, five editorials and seven items of correspondence, while one publication reported two studies. Three articles pertained to transcutaneous application of pulsed radiofrequency. Of the two randomised controlled trials, one reported efficacy of the pulsed radiofrequency while the other reported it to be ineffective. The majority of the uncontrolled and observational studies reported clinical efficacy of pulsed radiofrequency, however many of these studies had limitations. Further randomised controlled clinical trials are recommended in order for the practising pain physician to clearly understand the role of pulsed radiofrequency in the treatment of various chronic pain syndromes.

The objectives of the study were to study the incidence of various degrees of severity of thrombocytopenia in septic shock, the risk factors for its development and the correlation with clinical outcome. Complete blood counts, chemistry panel, arterial lactate, serum cortisol, APACHE II score, logistic organ dysfunction score and SOFA score were determined in 69 septic shock patients within 24 hours of admission or onset of septic shock. We followed the patients until they died or for six months to determine the mortality rate. The incidence of thrombocytopenia in our study group was 55%. Patients with thrombocytopenia had significantly higher serum creatinine, SOFA score, vasopressor requirement, lower P_aO₂/FiO₂ ratio and higher mortality than those without thrombocytopenia (P <0.05). Higher SOFA score, low P_aO₂/FiO₂ ratio and high vasopressor dose were independent risk factors for development of thrombocytopenia. The presence of thrombocytopenia had significant correlation with SOFA score (P=0.008). On receiver-operator characteristic curve analysis, platelet count was found to be predictive of increased mortality (area under curve=0.56). Thrombocytopenic patients had 1.4 times the risk of mortality and lower survival probability at six months (log rank test P=0.03). In conclusion, thrombocytopenia is common in septic shock and is associated with worse clinical outcome. Higher SOFA score, low P_aO₂/FiO₂ ratio and high vasopressor dose are independent risk factors for development of thrombocytopenia in septic shock.

Drug abuse is a significant social problem that can lead to serious obstetric complications, some of which may be confused with pregnancy-related disease states. Substance abuse poses a number of challenges with respect to the management of pain and the conduct of anaesthesia in the peripartum period.

This review was based on information from a literature search of epidemiological, research and review papers on substance abuse during pregnancy, obtained for the purpose of preparing a background paper for the Ministerial Council on Drug Strategy, Commonwealth Government of Australia.

Given that almost 80% of substance-abusing parturients require anaesthetic services in the perinatal period, early antenatal referral for anaesthetic review is recommended. To optimise the care of these vulnerable patients, obstetricians, general practitioners and midwives should attempt to identify substance-abusing parturients and refer them to an anaesthetist. A careful anaesthetic evaluation with non-judgemental questioning is essential, with management tailored to individual patient needs and the urgency of obstetric intervention for vaginal delivery or caesarean section.

Opioid-dependent women, in particular, benefit from antenatal pain management planning. Patients recovering from drug addiction should also have a well-documented analgesic strategy. A multidisciplinary approach will involve obstetricians, anaesthetists and staff of the Drug and Alcohol Service. In acute admissions of women by whom antenatal care was not accessed, a high index of suspicion for illicit drug use should arise. Because illicit substance use is so prevalent, if untoward reactions occur during an otherwise uneventful anaesthetic, the possibility of drug abuse should be considered.

Malignant hyperthermia is a pharmacogenetic disorder caused by autosomal dominant mutations in the ryanodine receptor type 1 gene. Propofol has been reported as a safe anaesthetic for malignant hyperthermia susceptible patients but has not been tested on cultured cells from patients with the ryanodine receptor type 1 mutation. The aim of this study was to determine whether propofol could trigger abnormal calcium fluxes in human myotubes isolated from malignant hyperthermia susceptible patients harbouring the native ryanodine receptor type 1 mutation. Muscle specimens were obtained from the patients to diagnose malignant hyperthermia disposition and the calcium-induced calcium release test and molecular genetic analyses were performed. Using the calcium sensitive probe Fura 2, we determined the 340/380 nm wavelength ratios by measuring alterations in calcium homeostasis in isolated myotubes from cultured skeletal muscle specimens. Two patients, one with ryanodine receptor type 1 R2508C and one with the L4838V mutation had accelerated calcium-induced calcium release rates. The 340/380 nm ratios increased when the propofol concentration exceeded 100 μM. The half-maximal activation concentrations (EC) for propofol from patients 1 and 2 were 181.1 and 420.5 μM, respectively. Increases in calcium concentrations in response to propofol dosage were limited to doses at least 100-fold greater than those used in clinical settings. These observations correlate well with clinical observations that propofol does not trigger malignant hyperthermia in susceptible humans.

In 144 patients who were referred to an anaesthetic allergy clinic because of perceived risk of anaphylaxis during anaesthesia, the only ‘at risk’ group that could be identified was patients with a history of unexplained severe adverse reaction during previous anaesthesia. Twenty-two of 45 patients with such a history had positive skin tests to an anaesthetic drug. Twenty-one positive tests were to neuromuscular blocking drugs and one to an opiate. In 18 of these patients the medical records were available and an adverse event had been recorded consistent with anaphylaxis. On the contrary, investigation of patients without a previous adverse reaction did not appear to be of value. These findings suggest that those patients with a history of a severe undiagnosed adverse event during previous anaesthesia should be investigated with preoperative skin-testing before undergoing further elective surgery.

The USCOM (Ultrasonic Cardiac Output Monitors) device is a noninvasive cardiac output monitor, which utilises transaortic or transpulmonary Doppler flow tracing and valve area estimated using patient height to determine cardiac output. We evaluated USCOM against thermodilution cardiac outputs and transoesophageal echocardiography valve area measurements in 22 ASA PS4 cardiac surgical patients. Data collection commenced following pulmonary artery catheter insertion, with cardiac output measurements repeated after sternotomy closure. Failure to obtain transaortic Doppler readings using USCOM occurred in 5% of planned measurements. USCOM transaortic analysis was not planned for 11 patients with known aortic disease. Bias at the aortic window (n = 20) was -0.79 l/min with limits of agreement from -3.66 to 2.08 l/min. At the pulmonary window, failure to obtain Doppler readings occurred in 24% of planned measurements. Bias at the pulmonary window (n=36) was -0.17 l/min with limits of agreement from -3.30 to 2.97 l/min. The USCOM estimates of valve area based on height showed poor correlation with the echocardiographic measurements of aortic and pulmonary valves (r=0.57 and r=0.17, respectively). It was concluded that USCOM showed poor agreement with thermodilution. The estimated valve area was identified as one source of error.

Increasing evidence indicates that mitochondrial dysfunction plays an important role in modulating the development of septic shock. In the present study, we investigated whether continuous venovenous haemofiltration (CVVH) with high-volume might improve myocardial mitochondrial dysfunction in a porcine model of peritonitis-induced septic shock. Sixteen male Landrace pigs weighing 31 ±5 kg were randomly assigned to normal control group (n=4), peritonitis group (n = 6) and peritonitis plus CVVH group (n = 6). All animals were anaesthetised and mechanically ventilated. After baseline examinations, the peritonitis group and the peritonitis plus CVVH group underwent induction of peritonitis. One hour later, the animals in the peritonitis plus CVVH group received treatment with high-volume CWH. Twelve hours after treatment, the animals were sacrificed. Animals in the peritonitis group were killed 13 hours after induction of peritonitis. Peritonitis challenge induced septic shock associated with increased blood lactate and high-volume CVVH improved lactate acidosis. Compared with the peritonitis group, cardiac output, stroke volume and mean arterial pressure were better maintained in peritonitis plus CVVH group. More importantly, high-volume CVVH improved myocardial mitochondrial complex I activity (0.22 ± 0.03 vs. 0.15 ± 0.04, P = 0.04). These results suggest that high-volume CVVH improves haemodynamics and heart dysfunction in septic shock and the improvement may be attributed to amelioration of myocardial mitochondrial dysfunction.

This study examined the incidence of hyperamylasaemia, in the absence of other plausible causes of pancreatic dysfunction, in intensive care unit (ICU) patients who received propofol.

One-hundred-and-seventy-two consecutive patients of a general ICU who stayed for more than 24 hours were studied. Patients with a diagnosis consistent with elevated serum amylase levels at admission were excluded from the study, as were patients who had received medications known to raise serum amylase levels. Forty-four patients 53 ± 20 years of age and median duration of ICU stay of five days (range two to 55) were eligible. Thirty of those, aged 54 ± 21 years and median duration of ICU stay of five days (range two to 27) received continuous infusion of propofol for sedation (maximum dose 45 μg/kg/min).

Of the 30 patients who received propofol, 16 (53%) developed hyperamylasaemia (125 to 466 IU/l) after two to nine days of continuous infusion. Liver and kidney function remained normal throughout the observation period. Of the 14 patients who did not receive propofol (aged 51 ± 18 years), only two (14%) developed hyperamylasaemia, a significantly lower incidence (P=0.021).

Propofol infusion is associated with biochemical evidence of pancreatic injury. Amylase levels monitoring of propofol-sedated patients is warranted.

The objective of this study was to compare the effects on regional blood flow and regional oxygen delivery of 4% succinylated gelatin solution (Gelofusine®, B. Braun) with those of normal saline. This was a randomised, controlled, crossover large animal study, which took place at the animal laboratory of university physiology institute. The subjects were seven merino cross-ewes.

We implanted flow probes around the aorta, coronary, renal and mesenteric arteries. We randomised animals to observation (control), normal saline (one litre over 15 minutes) or Gelofusine^* (one litre over 15 minutes). We measured central haemodynamics, organ blood flows, arterial blood gases and haemoglobin every 30 minutes for 210 minutes.

Compared to control, both Gelofusine^* and normal saline significantly and similarly increased mean arterial pressure, stroke volume, cardiac output and central venous pressure in the first hour (P <0.05). Such changes, however, were transient except for the increase in cardiac output seen with Gelofusine®. Normal saline significantly increased mesenteric blood flow in the first hour (P <0.05), while Gelofusine^* caused a specific, sustained and progressive increase in renal blood flow and conductance (P <0.05). Both fluids increased urine output and creatinine clearance (P <0.05), but, due to haemodilution, both decreased renal oxygen delivery in the first hour (P <0.05).

Normal saline and Gelofusine® have transient, volume expansion-related systemic haemodynamic effects, which are greater for Gelofusine®. Saline had a more pronounced early effect on mesenteric blood flow, while Gelofusine^* had a sustained and progressive greater effect on renal blood flow. The transient increase in urine output and creatinine clearance seen with both fluids occurred while renal oxygen delivery decreased.

Undetected intravenous placement of epidural catheters is rare but potentially fatal and no perfect identification method exists. Epidural catheters may be flushed before insertion to identify faulty epidural catheters, or to prime the system with local anaesthetic. We hypothesised that flushing epidural catheters before insertion may delay the detection of intravenous placement. We investigated our theory using both in vitro and in vivo models. The in vitro component examined flowrates in flushed and unflushed epidural catheters, using conditions designed to mimic epidural venous pressure. The in vivo component examined the flow within flushed and unflushed epidural catheters inserted into the forearm veins of 20 anaesthetised patients, using a randomised crossover design. The endpoint utilised for both components was the time taken for frank blood to reach the 20 cm mark on the epidural catheter. Blood flow to the 20 cm mark on the epidural catheter was significantly faster in the unflushed catheters than the flushed catheters, both in vitro and in vivo (in vitro, unflushed median = 18.6 s (range: 18.0 to 20.5 s), flushed 37.6 s (32.6 to 91.2 s), P=0.0009; in vivo, unflushed 9.2 seconds (range 5.0 to 35.3 s), flushed 19.2 s (10.6 to 47.4 s), P=0.003 in vivo). Flushed catheters also demonstrated a greater variability in the range of flowrates. Flushing epidural catheters before insertion may delay the detection of intravenous placement.

Drug-eluting stents are a recommended treatment for lesions in the coronary arteries. Stent insertion requires the patient remain on antiplatelet medication for a minimum of six months after insertion. A serious consequence of ceasing antiplatelet medication is late stent thrombosis leading to myocardial infarction in the territory of the drug-eluting stent. Continuing antiplatelet medication can lead to excessive bleeding at the time of surgery. Understanding the risk of complications attributable to bleeding or myocardial ischaemia will help in defining the optimal management of these patients at the time of noncardiac surgery.

This study is a retrospective database analysis and case note review of all patients with drug-eluting stents presenting for noncardiac surgical procedures over a three-year period in one centre.

Twenty-four patients with drug-eluting stents inserted presented for 43 noncardiac surgical procedures. Severe bleeding problems were encountered in one case. Three of 15 patients (20%) who ceased clopidogrel prior to surgery without alternative anti-thrombotic prophylaxis suffered myocardial infarction due to stent thrombosis. Four patients who received alternative anti-thrombotic prophylaxis did not suffer complications. All 19 patients who ceased clopidogrel remained on aspirin prior to surgery.

Patients treated with drug-eluting stents for coronary artery stenosis represent a challenging group of patients for subsequent perioperative management. The risk of myocardial infarction when clopidogrel is stopped prior to surgery is 20%, if alternative anti-thrombotic prophylaxis is not used. This risk persists beyond one year after insertion of drug-eluting stents. Some treatments appear to be effective in reducing the risk of myocardial infarction.

This study compared the efficacy of two different injection sites for subconjunctival anaesthesia (SCA) in cataract surgery. One-hundred-and-three eyes of 99 consecutive patients undergoing routine cataract surgery were randomised to receive SCA either to the superior bulbar conjunctiva (n=52) or the inferior bulbar conjunctiva (n=51). Pain experienced during anaesthetic administration and at various stages of the perioperative period was assessed using a simplified scale. Assessment of subconjunctival haemorrhage and chemosis was made by the surgeon. The percentage of patients reporting any pain on administration of superior SCA was 46% compared to 67% with inferior SCA (P=0.036). Moderate to severe pain on SCA injection was experienced by 15% and 18% of those in the superior and inferior SCA groups respectively. The cataract procedure was well tolerated in both groups. There was no difference between the groups for duration of surgery (P =0.25), anaesthetic related complications including chemosis (P =0.28), subconjunctival haemorrhage (P=0.38) or intraoperative complications (P =0.50).

We found that subconjunctival anaesthesia is effective for routine cataract surgery. There was no difference in block efficacy between superiorly and inferiorly delivered SCA. However, superior SCA appeared to be less painful on injection compared to inferiorly delivered SCA.

We assessed whether a modified fascia iliaca compartment block in unilateral total hip arthroplasty provides a morphine-sparing effect in the first 24 hours. This involved a randomised, double blind study of 44 patients. Both groups received a modified fascia iliaca block with the trial group receiving 30 ml 0.5% bupivacaine with 1:200,000 adrenaline, 150 μg clonidine and 9 ml 0.9%> saline and the control group receiving 40 ml 0.9% saline. Otherwise both groups received identical care with a subarachnoid block for operative anaesthesia. Patient-controlled morphine analgesia was commenced postoperatively and data were collected at three, six, 12 and 24 hours post commencement of surgery. We found that the trial group used less morphine at 12 and 24 hours (P <0.001). The median morphine usage at 24 hours was 37.5 mg in the control patients and 22 mg in the trial patients. Pain scores were similar between groups. We conclude that a modified fascia iliaca compartment block has a significant morphine-sparing effect in unilateral total hip arthroplasty.

Accidental endobronchial intubation is reported frequently during laparoscopic gynaecological surgery. We performed a prospective randomised study to compare three different methods of endotracheal tube placement in terms of susceptibility of accidental endobronchial intubation in patients undergoing laparoscopic gynaecologic surgery.

The endotracheal tube was positioned by one of three methods: it was secured by palpating at the suprasternal notch while holding the pilot balloon (Group); by placing the 21 cm mark at the upper incisors (Group_21cm); or by placing a guide mark, which was made on the surface of the tube 2 cm above the proximal end of the cuff, at the level of the vocal cords (Group_VC). The distance from the tip of endotracheal tube to the carina was measured with the patient in a neutral position (D_TC0) and after the formation of pneumoperitoneum in the Trendelenburg position (D_TC1).

Eighty-eight patients were enrolled. Pneumoperitoneum and Trendelenburg position caused inward movement of the endotracheal tube toward the carina in 99%. In each group, the mean value of D_TC1 was significantly shorter than D_TC0 (Group _Cuff 3.0 ± 1.1 vs. 1.7 ± 1.0, Group_21cm2.5 ± 0.8 vs. 1.1 ± 0.9, Group_vc 3.5 ± 0.7 vs. 2.3 ± 0.8, D_Tc0 vs. D_TC1 respectively)(all P <0.01). Accidental endobronchial intubation occurred in 14%, with the lowest frequency in Group_vc (2.6 %, P <0.01) and the highest in Group_21cm, although this was not significantly (P=0.09) different from Group_Cuff (26.7% vs. 10.0%).

The incidence of endobronchial intubation was lowest in Group_vc but endobrochial intubation could not be avoided using any of these methods.

Myringotomy with ventilation tube insertion in children involves turning the head from neutral to allow surgical access to the ear. In adults, rotation of the head from the midline generally increases the oropharyngeal leak pressure when a ProSeal™ laryngeal mask airway (PLMA) is used to manage the airway. There are concerns that these manoeuvres may distort or obstruct the paediatric airway. Paediatric sizes (1.5, 2.0 and 2.5) of the PLMA differ from the adult versions in that they do not have a dorsal cuff. This study examines the effect of these head position changes on the seal of the PLMA in children. Twenty-nine children (ASA 1-2, aged 0.9 to 7.5 years) scheduled for myringotomy were recruited. After PLMA insertion, oropharyngeal leak pressure and fibreoptic determined PLMA position scores were measured in the neutral position and with head rotation of 45° to the left or right. Fibreoptic positioning scores were similar in all positions. Head rotation was associated with a statistically significant but modest increase in oropharyngeal leak pressure versus the neutral position (P <0.05). After rotating the head from neutral, 38% (11 of 29) of subjects had an increase of oropharyngeal leak pressure of at least 2 cmH₂O. Only 7%> (2 of 29) of subjects had a decrease in oropharyngeal leak pressure with head rotation, the maximum decrease being 2 cmH₂O. Airway obstruction did not occur in any of the positions. We conclude that the efficacy of the seal for the pediatric sizes PLMA is improved by head rotation for myringotomy.

Despite strong arguments in favour of centralising care of critically ill children to paediatric intensive care units, around 2000 children per year are cared for in non-paediatric intensive care units in Australia and New Zealand. This paper reports a survey of consultants from 13 such units that admitted over 50 children in 2002 and 2003, to find out what factors affect the decision to keep critically ill children locally or transfer them to a paediatric intensive care unit and what infrastructure existed to support local care of these children. The results of this survey form the basis for a proposal to improve care of critically ill children in the non-paediatric intensive care units. The four key elements of this proposal are: the use of protocols, routine consultation with the regional paediatric intensive care unit, the use of telemedicine, and enhancing skills and experience of local staff. Evidence supporting these measures as well as the evidence for centralising care of critically ill children is reviewed.

Intensive care unit patients are at particular risk of respiratory failure after major abdominal surgery. Non-invasive ventilation or application of continuous positive airway pressure through a face mask may stabilise respiratory function and avoid the need for endotracheal re-intubation. However, there are various contraindications to noninvasive ventilation and/or tracheal re-intubation, such as recent oesophageal anastomosis, anastomotic leakage or tracheal stenting for tracheo-oesophageal fistula. A specific management strategy consisting of continuous intratracheal jet ventilation to support spontaneous respiratory function is described in two patients with contraindications to noninvasive ventilation or mask continuous positive airway pressure after major oesophageal surgery.

A recurrent empyema over a three-month period ultimately presented as an empyema necessitans (an empyema pointing through the skin) due to Fusobacterium varium. The recurrence of the empyema was due to an animal vertebra aspirated, during a bar-room altercation, into the right main bronchus, mimicking an endobronchial tumour.

We report the case of a 25-year-old woman in the second trimester of pregnancy with acute respiratory distress syndrome associated with miliary tuberculosis. Delivery of the baby by caesarean section at 24 weeks gestation resulted in an immediate and sustained improvement in respiratory function and maternal survival. We believe this to be the first report suggesting a role for caesarean section, performed with the aim of an improvement in maternal respiratory function, at such an early point in pregnancy.

A super morbidly obese (230 kg, body mass index 76 kg/m²) patient presented to our service for a planned elective caesarean section for twin delivery. She subsequently underwent a non-elective caesarean section after normal working hours under combined spinal epidural anaesthesia with invasive monitoring. Complex cases such as this, especially in the obstetric setting, require thorough multidisciplinary planning, communication and expertise but can be safely and successfully performed in dedicated stand-alone centres.

Pupillary responses are a simple test commonly used as a predictor of outcome after severe brain injury. It is also common for clinicians to associate bilaterally absent pupillary responses with very poor prognosis. We report a series of cases of severely brain injured children with bilaterally absent pupillary responses who had favourable outcomes. From a group of 89 patients with brain injury, 32 had bilaterally absent pupillary responses and six (four with traumatic brain injury and two with infective brain injury) subsequently had favourable outcomes. This represents 18.8% of patients and should be a reminder to clinicians that the clinical sign of bilaterally absent pupillary responses is not always associated with a hopeless outcome.