Neuromuscular blocking agents for electroconvulsive therapy: a systematic review.

Electroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to induce generalised seizures for the treatment of selected psychiatric disorders. The clinical indications for ECT as an effective therapeutic modality have been considerably expanded since its introduction. Anaesthesia and neuromuscular blocking agents (NMBAs) are required to ensure patients' safety during ECT. The optimal dose of muscle relaxant for ECT reduces muscle contractions without inducing complete paralysis. Slight residual motor convulsive activity is helpful in ascertaining that a seizure has occurred, while total paralysis prolongs the procedure unnecessarily. Suxamethonium is commonly used, but nondepolarising NMBAs are indicated in patients with certain comorbidities. In this review, we summarise current concepts of NMBA management for ECT.

Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs.

BACKGROUND: Experimental studies of haemorrhagic shock have documented a superior haemodynamic response and a better outcome in female animals as compared with male controls. Such sexual dimorphism has, nevertheless, not been reported after circulatory arrest that follows exsanguination and shock. We aimed to study differences in cerebral injury markers after exsanguination cardiac arrest in pre-pubertal piglets. The hypothesis was that cerebral injury is less extensive in female animals, and that this difference is independent of sexual hormones or choice of resuscitative fluid. METHODS: Thirty-two sexually immature piglets (14 males and 18 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation, using three resuscitation fluid regimens (whole blood, hypertonic saline and dextran, or acetated Ringers' solution plus whole blood and methylene blue). Haemodynamic values, cellular markers of brain injury and brain histology were studied. RESULTS: After successful resuscitation, female piglets had significantly greater cerebral cortical blood flow, tended to have lower S-100beta values and a lower cerebral oxygen extraction ratio. Besides, in female animals, systemic and cerebral venous acidosis were mitigated. Female piglets exhibited a significantly smaller increase in neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in their cerebral cortex, smaller blood-brain-barrier (BBB) disruption and significantly smaller neuronal injury. CONCLUSION: After resuscitation from haemorrhagic circulatory arrest, cerebral reperfusion is greater, and BBB permeability and neuronal injury is smaller in female piglets. An increased cerebral cortical iNOS and nNOS expression in males implies a mechanistic relationship with post-resuscitation neuronal injury and warrants further investigation.

Differences in cerebral reperfusion and oxidative injury after cardiac arrest in pigs.

BACKGROUND: An investigation of the free radical scavenger sodium 2-sulfophenyl-N-tert-butyl nitrone (S-PBN) and the weak vasodilatator Tris buffer mixture (TBM) on cerebral cortical blood flow (CCBF) and the jugular bulb concentration of two eicosanoids, indicators of oxidative stress and inflammation, was undertaken in 30 anaesthetized piglets during cardiopulmonary resuscitation (CPR) and after restoration of spontaneous circulation (ROSC). METHODS: Thirty animals were subjected to 8 min of untreated circulatory arrest followed by 8 min of closed-chest CPR. During CPR, the animals were randomized to receive 60 mg/kg S-PBN, 1 mmol/kg TBM or 2 ml/kg normal saline (n = 10 in each group). Systemic haemodynamic variables, CCBF and jugular bulb plasma concentrations of 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha were measured. RESULTS: The CCBF during reperfusion after ROSC was greater in the TBM group than in the S-PBN group, the regression coefficient between CCBF and mean arterial blood pressure being lower in the S-PBN group than in the TBM group. The jugular bulb plasma concentration of 8-iso-PGF2alpha during the first 30 min after ROSC was greater in the TBM group than in the S-PBN group. Administration of TBM after vasopressin did not attenuate the pressor effect of vasopressin. CONCLUSION: Administration of S-PBN during CPR results in less cerebral oxidative stress, possibly by promoting normal distribution of cerebral blood flow.

Neurological outcome after experimental cardiopulmonary resuscitation: a result of delayed and potentially treatable neuronal injury?

BACKGROUND: In experimental cardiopulmonary resuscitation (CPR) aortic balloon occlusion, vasopressin, and hypertonic saline dextran administration improve cerebral blood flow. Free radical scavenger alpha-phenyl-N-tert-butyl-nitrone (PBN) and cyclosporine-A (CsA) alleviate neuronal damage after global ischemia. Combining these treatments, we investigated neurological outcome after experimental cardiac arrest. METHODS: : Thirty anesthetized piglets, randomly allocated into three groups, were subjected to 8 min of ventricular fibrillation followed by 5 min of closed-chest CPR. The combined treatment (CT) group received all the above-mentioned modalities; group B was treated with balloon occlusion and epinephrine; and group C had sham balloon occlusion with epinephrine. Indicators of oxidative stress (8-iso-PGF(2 alpha)), inflammation (15-keto-dihydro-PGF(2 alpha)), energy crisis (hypoxanthine and xanthine), and anoxia/hypoxia (lactate) were monitored in jugular bulb venous blood. Neurological outcome was evaluated 24 h after CPR. RESULTS: : Restoration of spontaneous circulation (ROSC) was more rapidly achieved and neurological outcome was significantly better in the CT group, although there was no difference in coronary perfusion pressure between groups. The jugular venous PCO2 and cerebral oxygen extraction ratio were lower in the CT group at 5-15 min after ROSC. Jugular venous 8-iso-PGF(2 alpha) and hypoxanthine after ROSC were correlated to 24 h neurological outcome CONCLUSIONS: : A combination of cerebral blood flow promoting measures and administration of alpha-phenyl-N-tert-butyl-nitrone and cyclosporine-A improved 24 h neurological outcome after 8 min of experimental normothermic cardiac arrest, indicating an ongoing neuronal injury in the reperfusion phase.

Differences in the pharmacodynamics of epinephrine and vasopressin during and after experimental cardiopulmonary resuscitation.

Vasopressin has been investigated as a possible alternative to epinephrine during cardiopulmonary resuscitation (CPR). We tested the hypothesis that vasopressin, in comparison with epinephrine, would improve cerebral blood flow and metabolism during CPR as well as after restoration of spontaneous circulation (ROSC). A total of 22 anaesthetised piglets were subjected to 5 min of ventricular fibrillation followed by 8 min of closed-chest CPR. The piglets were randomly allocated to receive repeated boluses of either 45 microg/kg epinephrine or 0.4 U/kg vasopressin IV. Haemodynamic parameters, cerebral cortical blood flow and cerebral tissue pH and PCO(2) were continuously monitored during CPR and up to 4 h after ROSC. Cerebral oxygen extraction ratio was calculated. Cerebral cortical blood flow increased transiently after each bolus of epinephrine, while only the first bolus of vasopressin resulted in a sustained increase. The peak in cerebral cortical blood flow was reached approximately 30 s later with vasopressin. During the initial 5 min following ROSC, cerebral cortical blood flow was greater in the vasopressin group. In conclusion, there is a difference between epinephrine and vasopressin in the time from injection to maximal clinical response and the duration of their effect, but their overall effects on blood pressures and cerebral perfusion do not differ significantly during CPR. In contrast, vasopressin results in a greater cerebral cortical blood flow during a transient period after ROSC.

Improved cerebral blood supply and oxygenation by aortic balloon occlusion combined with intra-aortic vasopressin administration during experimental cardiopulmonary resuscitation.

BACKGROUND: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to improve myocardial and cerebral blood flow. Aortic balloon occlusion during CPR may also augment myocardial and cerebral blood flow and can be used as a central route for the administration of resuscitative drugs. We hypothesized that, as compared with intravenously administered vasopressin, the administration of this drug above the site of an aortic balloon occlusion would result in a greater increase in cerebral perfusion and oxygenation during CPR and after restoration of spontaneous circulation (ROSC). METHODS: Twenty piglets were subjected to 5 min of ventricular fibrillation followed by 8 min of closed-chest CPR and were treated with 0.4 U kg(-1) boluses of vasopressin intravenously (the IV-vasopressin group with sham aortic balloon) or above the site for an aortic balloon occlusion (the balloon-vasopressin group). The aortic balloon catheter was inflated in the latter group 1 min after commencement of CPR and was deflated within 1 min after ROSC. Systemic blood pressures, cerebral cortical blood flow, cerebral tissue pH and PCO2 were monitored continuously and the cerebral oxygen extraction ratio was calculated. RESULTS: During CPR, arterial blood pressure and cerebral perfusion pressure were greater in the balloon-vasopressin group, as compared with the IV-vasopressin group. These pressures did not differ between the groups after ROSC. Cerebral cortical blood flow was not significantly greater in the balloon-vasopressin group during CPR, whereas significantly higher cortical blood flow levels were recorded after ROSC. Cerebral tissue pH decreased in the IV-vasopressin group during the post-resuscitation hypoperfusion period. In contrast, decreasing pressures during the hypoperfusion period did not result in increasing tissue acidosis in the balloon-vasopressin group. CONCLUSIONS: During CPR, intra-aortic vasopressin combined with aortic balloon occlusion resulted in significantly greater perfusion pressures but not in greater cerebral cortical blood flow. After ROSC, however, a greater increase in cortical blood flow was recorded in the balloon-vasopressin group, even though the aortic balloon was deflated and perfusion pressures did not differ between the groups. This suggests that vasopressin predominantly gives vasoconstrictive effects on cerebral cortical vessels during CPR, but results in cerebral cortical vasodilatation after ROSC.

Intra-aortic administration of epinephrine above an aortic balloon occlusion during experimental CPR does not further improve cerebral blood flow and oxygenation.

Balloon occlusion of the descending aorta during cardiopulmonary resuscitation (CPR) improves coronary and cerebral blood flow. In comparison with an equivalent dose administered through a central venous catheter it has been suggested that epinephrine administration above the aortic occlusion might produce a more rapid increase in coronary perfusion pressure and a shorter time to restoration of spontaneous circulation (ROSC). In a recent study, however, outcome was not improved after intra-aortic epinephrine administration. We hypothesised that epinephrine administered above the aortic occlusion could impose adverse effects on cerebral blood flow and oxygenation, possibly because of an alpha-adrenergic mediated vasoconstriction in the cerebral vascular beds. Twenty-six piglets underwent 5 min of non intervention cardiac arrest followed by 8 min of closed-chest CPR. They were randomised to receive bolus doses of 45 microg/kg epinephrine either above the aortic occlusion or through a central venous catheter. Cerebral cortical blood flow was continuously measured using laser-Doppler technique. Cerebral tissue pH and PCO(2) were also measured using a multi-parameter fiberoptic device and cerebral oxygen extraction was calculated. Balloon inflation resulted in an immediate enhancement of cerebral cortical blood flow. Each of the epinephrine boluses through the central venous catheter resulted in a transient increase in cerebral cortical blood flow. When administered above the aortic balloon occlusion, epinephrine did not result in a further increase in cerebral cortical blood flow, though a significant increase in cerebral perfusion pressure was recorded throughout the CPR period. Cerebral tissue pH monitoring revealed severe acidosis during CPR and long after ROSC, which was refractory to buffering. No differences in the cerebral oxygen extraction ratio were observed between the groups. In conclusion, epinephrine administration above an aortic balloon occlusion was unable to improve cerebral blood flow and oxygenation. In fact, it may even attenuate the beneficial effects of aortic balloon occlusion on cerebral blood flow due to an alpha-adrenergic mediated cerebral vasoconstriction. Further studies, including dose-response and volumes of distribution, are needed to identify the effective beneficial dosage of epinephrine during aortic occlusion with the least possible adverse effects.

Development of a novel biomarker of free radical damage in reperfusion injury after cardiac arrest.

In a porcine model of cardiopulmonary resuscitation (CPR), we investigated changes in the plasma levels of 8-iso-PGF(2alpha), a marker for oxidative injury, and 15-keto-dihydro-PGF(2alpha), an inflammatory response indicator during the post-resuscitation period after cardiac arrest. Twelve piglets were subjected to either 2 or 5 min (VF2 and VF5 group) of ventricular fibrillation (VF) followed by 5 min of closed-chest CPR. Six piglets without cardiac arrest were used as controls. In VF5 group, 8-iso-PGF(2alpha) in the jugular bulb plasma (draining the brain) increased four-fold. Jugular bulb 8-iso-PGF(2alpha) in the control group remained unchanged. The 15-keto-dihydro-PGF(2alpha) also increased four-fold in the VF5 group. Thus, 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) measurements in jugular bulb plasma may be used as biomarkers for quantification of free radical catalyzed oxidative brain injury and inflammatory response in reperfusion injury.

Maximisation of cerebral blood flow during experimental cardiopulmonary resuscitation does not ameliorate post-resuscitation hypoperfusion.

Continuous intra-aortic balloon occlusion has been reported to improve cerebral blood flow during cardiopulmonary resuscitation (CPR) but not to ameliorate the impaired blood recirculation occurring after restoration of spontaneous circulation (ROSC). Volume expansion with hypertonic solutions may improve recovery of brain function by enhancing post-resuscitation cerebral blood flow. We hypothesised that the combination of these treatments with open-chest CPR would improve cerebral blood flow during CPR, and attenuate post-resuscitation flow disturbances. In 32 anaesthetised piglets, catheters were placed for haemodynamic and blood gas monitoring. Open-chest CPR was initiated after 9 min of ventricular fibrillation. The piglets were treated either with 3 ml kg(-1) hypertonic saline and dextran (HSD) (n = 10), HSD and balloon occlusion (n = 10) or with normal saline (n = 12). After 7 min of CPR, internal defibrillatory shocks were administered to restore spontaneous circulation. Haemodynamic variables, continuous cerebral cortical blood flow, cerebral tissue pH and pCO2 and blood gas parameters were measured during CPR and up to 210 min after ROSC. Higher cerebral perfusion pressure was found in the balloon-HSD group during CPR. This group exhibited less arterial hypertension immediately after ROSC compared with the other groups. Thereafter, a fairly rapid decrease of the perfusion pressures was observed in all groups reaching a minimum level approximately 30 min after ROSC. Cerebral cortical blood flow was significantly higher and cerebral oxygen extraction ratio significantly lower in the balloon-HSD group during CPR, but not after ROSC. In conclusion, a combination of intra-aortic balloon occlusion and HSD administration improves cerebral blood flow and brain oxygen supply during experimental open-chest CPR. In contrast, cerebral blood flow after ROSC was not shown to be influenced by this treatment.