Anaesthetic management of patients with severe sepsis.

Severe sepsis, a syndrome characterized by systemic inflammation and acute organ dysfunction in response to infection, is a major healthcare problem affecting all age groups throughout the world. Anaesthetists play a central role in the multidisciplinary management of patients with severe sepsis from their initial deterioration at ward level, transfer to the diagnostic imaging suite, and intraoperative management for emergency surgery. The timely administration of appropriate i.v. antimicrobial therapy is a crucial step in the care of patients with severe sepsis who may require surgery to control the source of sepsis. Preoperative resuscitation, aimed at optimizing major organ perfusion, is based on judicious use of fluids, vasopressors, and inotropes. Intraoperative anaesthesia management requires careful induction and maintenance of anaesthesia, optimizing intravascular volume status, avoidance of lung injury during mechanical ventilation, and ongoing monitoring of arterial blood gases, lactate concentration, haematological and renal indices, and electrolyte levels. Postoperative care overlaps with ongoing management of the severe sepsis syndrome patient in the intensive care unit. These patients are by definition, high risk, already requiring multiple supports, and require experienced and skilful decision-making to optimize their chances of a favourable outcome. Similar to acute myocardial infarction, stroke, or acute trauma, the initial hours (golden hours) of clinical management of severe sepsis represent an important opportunity to reduce morbidity and mortality. Rapid clinical assessment, resuscitation and surgical management by a focused multidisciplinary team, and early effective antimicrobial therapy are the key components to improved patient outcome.

Use of recombinant factor VIIa in massive post-partum haemorrhage.

BACKGROUND AND OBJECTIVE: Massive post-partum haemorrhage continues to be one of the world's leading causes of maternal morbidity and mortality. Any new treatment that potentially helps at risk parturients should be thoroughly investigated. Recombinant factor VIIa (rVIIa) is increasingly being used in the treatment of massive haemorrhage. We performed a case-matched analysis of its use since 2003 in the treatment of massive post-partum haemorrhage at our hospital. METHODS: Twenty-eight cases of massive post-partum haemorrhage were identified over a 3-yr period since 2003. In six of these cases, rVIIa was used as part of their management. Six case-matched controls were sought. The six women with the greatest requirement for packed red cell transfusion who also had a deranged prothrombin time were included. The groups were then compared for differences. The worst prothrombin time in each group was noted as was the best prothrombin time within 6 h, this was used as our measure of response to treatment. RESULTS: There was no statistical difference in age, gestation, parity, transfusion requirements, mode of delivery or the severity of the coagulopathy between the two groups. In both groups the prothrombin time improved with management. There was no significant difference in either the magnitude of the improvement in the value of the prothrombin time or the absolute value of the best prothrombin time (P = 0.09). Five out of the six women in the rFVIIa group had normal or low prothrombin times within 6 h yet only one woman who did not receive rFVIIa had a normal prothrombin time within 6 h though this was not significant (P = 0.08). CONCLUSIONS: This case-matched analysis supports the management of massive post-partum haemorrhage with appropriate resuscitation, surgical intervention and use of blood and blood products. This study does not support the routine use of rFVIIa in the management of massive obstetric haemorrhage. rFVIIa may have a role to play in this management but further studies and analyses will be required.

Effects of halothane and isoflurane on the intracellular Ca2+ transient in ferret cardiac muscle.

BACKGROUND: Halothane and isoflurane depress myocardial contractility by decreasing transsarcolemmal Ca2+ influx and Ca2+ release from the sarcoplasmic reticulum. Decreases in Ca2+ sensitivity of the contractile proteins have been shown in skinned cardiac fibers, but the relative importance of this effect in intact living myocardium is unknown. The aims of this study were to assess whether halothane and isoflurane decrease myofibrillar Ca2+ sensitivity in intact, living cardiac fibers and to quantify the relative importance of changes in myofibrillar Ca2+ sensitivity versus changes in myoplasmic Ca2+ availability caused by these anesthetics. METHODS: The effects of halothane and isoflurane (0-1.5 times the minimum alveolar concentration (MAC) in three equal increments) on isometric and isotonic variables of contractility and on the intracellular calcium transient were assessed in isolated ferret right ventricular papillary muscle microinjected with the Ca2+-regulated photoprotein aequorin. The intracellular calcium transient was analyzed in the context of a multicompartment model of intracellular Ca2+ buffers in mammalian ventricular myocardium. RESULTS: Halothane and isoflurane decreased contractility, time-to-peak force, time to half-isometric relaxation, and intracellular Ca2+ transient in a reversible, concentration-dependent manner. Halothane, but not isoflurane, slowed the increase and the decrease of the intracellular Ca2+ transient. Increasing extracellular Ca2+ in the presence of anesthetic to produce peak force equal to control values increased intracellular Ca2+ to values higher than control values. CONCLUSIONS: Halothane decreases myoplasmic Ca2+ availability more than isoflurane; halothane and isoflurane decrease myofibrillar Ca2+ sensitivity to the same extent; in halothane at 0.5 MAC and isoflurane at 1.0 MAC, the decrease in Ca2+ sensitivity is already fully apparent; halothane decreases intracellular Ca2+ availability more than myofibrillar Ca2+ sensitivity; and isoflurane decreases myoplasmic Ca2+ availability and Ca2+ sensitivity to the same extent, except at 1.5 times the MAC, which decreases Ca2+ availability more.

Preoperative or postoperative diclofenac for laparoscopic tubal ligation.

We have compared the analgesic effects of diclofenac given before operation or immediately after operation in a randomized, double-blind, double-dummy study of 40 healthy female patients undergoing laparoscopic tubal ligation. Group 1 patients received diclofenac 75 mg as a 3-ml i.m. injection 1-2 h before operation and normal saline 3 ml i.m. immediately after surgery. Group 2 patients received normal saline 3 ml i.m. before operation and diclofenac 75 mg i.m. immediately after surgery. Outcome measures were patients' perception of pain on a visual analogue scale (VAS), verbal response scale (VRS), the number of patients who required postoperative morphine, time to first postoperative morphine injection and total dose of morphine given. VAS at 30 min and at 1, 3 and 6 h after operation were, respectively (median, interquartile range) 4.5 (2.3-6.0) vs 5.3 (2.8-7.8); 3.3 (2.3-5.0) vs 4.4 (3.0-5.8); 1.4 (0-2.3) vs 1.9 (0.8-3.0); 0.5 (0-1) vs 0.7 (0-1.3), (ns). VRS at 1 and 3 h after operation were, respectively, (median, interquartile range) 2.2 (1.5-3.0) vs 2.7 (2.0-4.0) and 0.8 (0-1.3) vs 0.9 (0-1.5) (ns). Sixteen patients in group 1 compared with 17 in group 2 required postoperative morphine. Time to first morphine administration and dose given were, respectively, (median, interquartile range) 50.6 (39-60) min vs 35.7 (20-49) min (P = 0.1) and 9.0 (5-10) mg vs 9.5 (7.5-10) (P = 0.9).(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: At Rotunda Hospital in Dublin, Ireland, a randomized double-blind, double-dummy study of 40 women undergoing laparoscopic tubal ligation was conducted to examine the preoperative and postoperative analgesic effects of 75 mg intramuscular (i.m.) diclofenac, a nonsteroidal anti-inflammatory drug. 20 women first received 75 mg diclofenac 1-2 hours before tubal ligation and normal saline right after the operation. The other 20 women received the same injections in the reverse order. As outcome measures, researchers used patients' perception of pain on a visual analogue scale (VAS), verbal response scale (VRS), number of patients who needed a postoperative 10 mg morphine injection, time to first postoperative morphine injection, and total dose of morphine administered. The median pain scores on VAS were essentially the same at 30 minutes and at 1, 3, and 6 hours after the operation. The median pain scores on VRS were also the same at 1 and 3 hours after the operation. The median dose of morphine was less than 10 mg in both groups. Four women in the first group and three women in the second group did not require analgesia. Even though the median time to first morphine injection was longer for the first group than the second group (50.6 vs. 35.7 min), the difference was not statistically significant (p = 0.1). These findings show that diclofenac does not provide pre-emptive analgesia in patients undergoing laparoscopic tubal ligation.

Role of transsarcolemmal Ca2+ entry in the negative inotropic effect of nitrous oxide in isolated ferret myocardium.

The purpose of this study was to investigate the effects of nitrous oxide (N2O) on transsarcolemmal calcium influx in isolated ferret right ventricular myocardium. Using a range of loading conditions, papillary muscles were equilibrated in 50% nitrogen (N2) or 50% N2O in oxygen in the presence and absence of ryanodine, a specific inhibitor of calcium release from the sarcoplasmic reticulum. After equilibration in 50% N2O or 50% N2 in oxygen, peak developed force, peak isotonic shortening, and maximal unloaded velocity of shortening were compared in the presence and absence of 10(-6) M ryanodine. Fifty percent N2O caused a significant reduction in contractility in control conditions and a further significant reduction in contractile variables in the presence of 10(-6) M ryanodine. We conclude that at least part of the negative inotropic effect of N2O is due to an inhibition of transsarcolemmal calcium influx.

Ratio of hepatic arterial-to-portal venous blood flow--validation of radionuclide techniques in an animal model.

The ratio of hepatic arterial-to-portal venous blood flow can be determined from the analysis of a first-pass bolus through the liver by a number of techniques. This study examines the validity of four radiotracer techniques in an animal model. Thirty-four flow studies (3 mCi 99mTc-DTPA/study) were performed in seven anesthetized pigs. Images were acquired for 200 sec and time-activity curves were generated from lung, liver and kidney ROIs. These curves were analyzed using a slope-based (HPI), a height-based (mHAR) and two deconvolution-based methods employing exponential or gamma variate fits. There was an excellent correlation (r greater than 0.9) between results obtained with flow probes and the radiotracer techniques, with the exception of the HPI technique (r = 0.75). The mHAR and deconvolution techniques were inaccurate at very low and high arterial flows, due respectively to noise limitations and hemodynamic instability in the animal. Nevertheless, these techniques appear to be the most promising for routine clinical use.

Mechanism of the positive inotropic effect of ketamine in isolated ferret ventricular papillary muscle.

Ketamine is a cardiovascular stimulant through its sympathomimetic effects; however, its direct inotropic effect has been reported as positive in rat and negative in rabbit ventricular myocardium. This study reexamines the effect of ketamine on the contractile properties of mammalian ventricular myocardium. In isolated, electrically stimulated ferret right ventricular papillary muscles, the authors assessed the inotropic effect of ketamine (10(-6) M to 3 x 10(-4) M in 0.5 log M increments) alone and in various pharmacologic conditions designed to delineate ketamine's site(s) of action. Ketamine exerted a positive inotropic effect that was maximal at 10(-4) M. Bupranolol (10(-7) M) abolished this positive inotropic effect, whereas phentolamine (10(-6) M) did not. Depletion of norepinephrine stores by reserpine also eliminated ketamine's positive inotropic effect, indicating that ketamine caused indirect activation of the beta-adrenoceptor. Ketamine did not exert a positive inotropic effect in the presence of simultaneous inhibition of neuronal norepinephrine uptake with desmethylimipramine (DMI) (5 x 10(-6) M) and extraneuronal uptake with corticosterone (5 x 10(-5) M). It is likely that ketamine's action is to inhibit norepinephrine uptake at the neuroeffector junction rather than to augment norepinephrine release. In the presence of corticosterone, ketamine exerted a smaller positive inotropic effect than that seen with ketamine alone. Ketamine produced a small increase in force development in the presence of DMI, but this did not reach statistical significance. Inhibition of neuronal catecholamine uptake appears to be the predominant mechanism of ketamine's positive inotropic effect.

Effects of nitrous oxide on contractility, relaxation and the intracellular calcium transient of isolated mammalian ventricular myocardium.

The effects of nitrous oxide on variables of contractility and relaxation were analyzed in isolated ferret right ventricular papillary muscles. Each mechanical variable, in isometric, isotonic, and zero-load-clamped twitches, was compared to the average value of that variable in control conditions (50% nitrogen in oxygen), before and after equilibration with 20%, 30% and 50% nitrous oxide in 50% oxygen. Nitrous oxide caused a concentration-dependent decrease in contractility under all loading conditions, with minor changes in relaxation. The intracellular calcium transient was detected with the Ca(++)-regulated photoprotein aequorin. The change in aequorin luminescence on exposure to nitrous oxide suggests that the negative inotropic effect of nitrous oxide is due to a decrease in calcium availability with no effect on myofibrillar responsiveness to calcium.