In vitro suppression of drug-induced methaemoglobin formation by Intralipid(®) in whole human blood: observations relevant to the 'lipid sink theory'.

To provide further evidence for the lipid sink theory, we have developed an in vitro model to assess the effect of Intralipid® 20% on methaemoglobin formation by drugs of varying lipid solubility. Progressively increasing Intralipid concentrations from 4 to 24 mg.ml⁻¹ suppressed methaemoglobin formation by the lipid soluble drug glyceryl trinitrate in a dose-dependent manner (p < 0.001). Both dose and timing of administration of Intralipid to blood previously incubated with glyceryl trinitrate for 10 and 40 min resulted in significant suppression of methaemoglobin formation (p < 0.0001 and p < 0.05, respectively). Mathematical modelling demonstrated that the entire process of methaemoglobin formation by glyceryl trinitrate was slowed down in the presence of Intralipid. Intralipid did not significantly suppress methaemoglobin formation induced by 2-amino-5-hydroxytoluene (partially lipid soluble) or sodium nitrite (lipid insoluble; both p > 0.5). This work may assist determination of the suitability of drugs taken in overdose for which Intralipid might be deployed.

Resuscitation in massive obstetric haemorrhage using an intraosseous needle.

A 38-year-old woman experienced a massive postpartum haemorrhage 30 minutes after emergency caesarean delivery. The patient became severely haemodynamically compromised with an unrecordable blood pressure. Rapid fluid resuscitation was limited by the capacity of the intravenous cannula in place at the time and inability to establish additional vascular access using conventional routes in a timely manner. An intraosseous needle was inserted in the proximal humerus at the first attempt and administration of resuscitation fluid by this route subsequently enabled successful placement of further intravenous lines. Blood and blood products were deployed in conjunction with intra-operative cell salvage and transoesophageal Doppler cardiac output monitoring was used to assess adequacy of volume replacement. Haemorrhage control was finally achieved with the use of recombinant factor VIIa and hysterectomy.

Sequential drug verification errors resulting in wrong drug administration during caesarean section.

An intravenous bolus of phentolamine was inadvertently given to a parturient during an emergency caesarean section following delivery of her infant when the intention had been to give an intravenous bolus of 5 IU Syntocinon. Root cause analysis identified a series of errors originating in the hospital pharmacy when one drug package was mistakenly issued in place of another. Subsequent checks failed to detect the original mistake. The final and most important check immediately before intravenous administration was also at fault. This case highlights a systems failure that permitted issue, transportation and administration of the wrong drug to a parturient. Robust measures to ensure avoidance of drug administration errors should be evaluated and introduced where possible.

Early treatment of a quetiapine and sertraline overdose with Intralipid.

We describe the initial management and subsequent recovery of a 61 year-old male patient following attempted suicide by oral ingestion of a potentially fatal overdose of quetiapine and sertraline. Intravenous Intralipid was given soon after initiation of basic resuscitation. There was a rapid improvement in the patient's level of consciousness. No other clinical signs of drug toxicity were observed. Intralipid may have reversed the deep coma associated with ingestion and prevented other manifestations of drug toxicity occurring, thus expediting this patient's recovery.

Co-induction of anaesthesia with 0.75 mg kg propofol followed by sevoflurane: a randomized trial in the elderly with cardiovascular risk factors.

BACKGROUND: The induction of general anaesthesia is associated with the greatest cardiovascular changes in elderly patients. Induction can be performed either intravenously or with gaseous induction. Sevoflurane has advantages over propofol for induction of anaesthesia in the elderly, since the lower reduction in mean arterial pressure with sevoflurane is both statistically and clinically significant. This prospective randomized controlled trial investigated the cardiovascular benefits of co-induction of anaesthesia with 0.75 mg kg(-1) propofol and 8% sevoflurane, when compared with 8% sevoflurane alone in patients requiring surgery for fractured neck of femur. METHOD: In total, 38 patients aged 75 or over were allocated into the two groups, receiving either 0.75 mg kg(-1) of propofol followed by 8% sevoflurane or 8% sevoflurane alone. Vital signs were recorded until successful insertion of a laryngeal mask. Induction times, induction events and patient satisfaction scores were also recorded. RESULTS: Results showed that there were no differences in the cardiovascular parameters between the two groups. Induction times were faster in the propofol and sevoflurane group (62 vs. 81 s; P = 0.028). The postoperative questionnaire showed that the majority of patients in both groups were satisfied with the induction process. CONCLUSIONS: We concluded that 0.75 mg kg(-1) of propofol followed by sevoflurane induction is an acceptable alternative to sevoflurane induction. It is associated with similar haemodynamic variables, faster induction times and is very well tolerated.

Nitric oxide modulation of pulmonary vascular resistance is red blood cell dependent in isolated rat lungs.

Nitric oxide (NO) or endothelium-derived relaxing factor may play an important role in modulating pulmonary vascular resistance (PVR), although previous studies have produced conflicting results. Endogenous NO inhibition causes an increase in PVR in intact animals but not in saline-perfused isolated lungs. We hypothesized that blood is essential for NO to serve as a modulator of PVR. Therefore, the effects of endogenous NO inhibition (N omega-nitro-L-arginine methyl ester [L-NAME]) were determined in isolated rat lungs as related to the presence of different blood components under normoxic conditions and after 1 wk of hypoxia (fraction of inspired oxygen [FIO2] = 10%). Exogenously administered inhaled NO was evaluated in isolated lungs from normoxic and hypoxic rats. In normoxic rats, L-NAME (10-100 microM) caused a dose-dependent increase in PVR in whole (hematocrit [Hct] 40%) and diluted (Hct 12%) blood-perfused lungs. L-NAME (10-800 microM) had no effect in isolated lungs perfused with a modified salt solution of equal viscosity to blood either alone, or containing plasma (50%) or free oxyhemoglobin (10 microM). In whole blood perfused lungs, L-NAME (100 microM) increased PVR more in hypoxic versus normoxic isolated lungs (141% vs 100%). Inhaled NO decreased PVR in isolated lungs from hypoxic rats and partially reversed the effects of L-NAME, but had no effect in normoxic lungs. In conclusion, endogenous and inhaled NO modulate PVR in isolated rat lungs and this role is increased by prolonged hypoxia. The response to inhibition of endogenous NO is dependent on the presence of red blood cells and is independent of the changes in viscosity or the presence of oxyhemoglobin or plasma.

The effects of needle type, gauge, and tip bend on spinal needle deflection.

Although the use of fine-gauge spinal needles reduces the incidence of postdural puncture headache, they are associated with increased risk of placement failure as a result of deflection and bending. This in vitro study quantifies spinal needle deflection from the axis of insertion with respect to needle type, gauge, and tip bend. In addition to straight-tip needles, those with standardized 5 degrees and 10 degrees tip bends were studied. The purpose was to examine the effect of tip bend, which has been described with small gauge spinal needles after bony contact, on needle path deflection. Needles studied included Quincke (Q), Sprotte (S), and Whitacre (W) in sizes ranging from 18-gauge to 29-gauge. Needles were inserted perpendicularly into porcine paraspinous muscle followed by radiologic investigation. Measurements of needle deflection from the axis of insertion at depths of 20, 40, and 60 mm were performed in a blinded fashion. Straight-tip Q needle deflection, but not W or S, was correlated with gauge and depth of insertion. Although there were differences within needle type groups, needle deflection was generally correlated with the degree of tip bend. We conclude that spinal needle deflection is dependent on the type of needle (W < S < Q), and that the magnitude of deflection is related to gauge (large < small) and tip bend (straight < 5 degrees < 10 degrees).

Regional anaesthesia for repeat Caesarean section in a patient with phantom limb pain.

The triggering of phantom limb pain by subarachnoid or epidural anaesthesia has been well described leading to the suggestion that neuraxial regional anaesthesia is relatively contraindicated in lower limb amputees. We report our experience of the provision of anaesthesia for repeat Caesarean section on two occasions in such a patient. Intrathecal fentanyl and morphine supplementation of bupivacaine successfully abolished peri-operative phantom limb pain, whereas epidural anaesthesia was associated with recurrence of phantom limb pain upon regression of the block.

Pre-emptive versus post-surgical administration of ketorolac for hysterectomy.

Seventy-seven women who underwent routine vaginal or abdominal hysterectomy were randomly allocated to receive intravenous ketorolac 30 mg either 30 min before surgical incision (pre-emptive group, n = 37), or at the end of the surgical procedure (post-surgical group, n = 40). The patients received routine post-operative care, which included morphine by patient-controlled analgesia, 1 mg per demand with a lockout of 6 min and a background infusion of 1 mg h-1. In addition, pain was assessed at 12 and 24 h using a 100 mm visual analogue scale (VAS), both at rest and on coughing. At 24 h, the median VAS at rest was 24 mm (range 0-80) in the pre-emptive group and 28 mm (range 0-100) in the post-surgical group. The average morphine consumption rate over the first 24 h was 1.9 mg h-1 (SD +/- 0.6) in the pre-emptive group, and 2.2 mg hr-1 (SD +/- 1.1) in the post-surgical group. There were no significant differences on univariate testing. Subsidiary stepwise multiple regression modelling identified age, weight, type of hysterectomy, and the timing of ketorolac administration as significant explanators of post-operative morphine consumption. A statistically significant pre-emptive analgesic effect was therefore identifiable, but the clinical significance is uncertain in relation to the other influences on post-operative analgesic requirements.