The impact on postoperative outcomes of intraoperative fluid management strategies during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The impact of intraoperative fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative outcomes has been poorly investigated. This study aimed to retrospectively evaluate the impact of intraoperative fluid management strategy on postoperative outcomes and survival. METHODS: 509 patients undergoing CRS and HIPEC at Uppsala University Hospital/Sweden 2004-2017 were categorized into two groups according to the intraoperative fluid management strategy: pre-goal directed therapy (pre-GDT) and goal directed therapy (GDT), where a hemodynamic monitor (CardioQ or FloTrac/Vigileo) was used to optimize fluid management. Impact on morbidity, postoperative hemorrhage, length-of-stay and survival was analyzed. RESULTS: The pre-GDT group received higher fluid volume compared to the GDT group (mean 19.9 vs. 16.2 ml/kg/h, p < 0.001). Overall postoperative morbidity Grade III-V was higher in the GDT group (30% vs. 22%, p = 0.03). Multivariable adjusted odds ratio (OR) for Grade III-V morbidity was 1.80 (95%CI 1.10-3.10, p = 0.02) in the GDT group. Numerically, more cases of postoperative hemorrhage were found in the GDT group (9% vs. 5%, p = 0.09), but no correlation was observed in the multivariable analysis 1.37 (95%CI 0.64-2.95, p = 0.40). An oxaliplatin regimen was a significant risk factor for postoperative hemorrhage (p = 0.03). Mean length of stay was shorter in the GDT group (17 vs. 26 days, p < 0.0001). Survival did not differ between the groups. CONCLUSION: While GDT increased the risk for postoperative morbidity, it was associated with shortened hospital stay. Intraoperative fluid management during CRS and HIPEC did not affect the postoperative risk for hemorrhage, while the use of an oxaliplatin regimen did.

Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest.

BACKGROUND: Long-term survival after cardiac arrest (CA) due to shock-refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets. METHODS: A total of 26 immature male piglets were subjected to 12-min VF followed by 8-min CPR. The treatment group (n=13) received i.v. (intravenous) boluses vasopressin 0.4 U/kg, esmolol 250 µg/kg and milrinone 25 µg/kg after 13 min, followed by i.v. boluses esmolol 375 µg/kg and milrinone 25 µg/kg after 18 min and continuous esmolol 15 µg/kg/h infusion during 180 min reperfusion, whereas controls (n=13) received equal amounts of vasopressin and saline. A 200 J monophasic counter-shock was delivered to achieve resumption of spontaneous circulation (ROSC) after 8 min CPR. If ROSC was not achieved, another 200 J defibrillation and bolus vasopressin 0.4 U/kg would be administered in both groups. Direct current shocks at 360 J were applied as one shot per minute over maximally 5 min. Hemodynamic variables and troponin I as a marker of cardiac injury were recorded. RESULTS: Troponin I levels after 180 min reperfusion were lower in the treatment group than in controls (P<0.05). The treatment group received less norepinephrine (P<0.01) and had greater diuresis (P<0.01). There was no difference in survival between groups. CONCLUSION: The combination of milrinone, esmolol and vasopressin decreased cardiac injury compared with vasopressin alone.

Adrenaline increases blood-brain-barrier permeability after haemorrhagic cardiac arrest in immature pigs.

BACKGROUND: Adrenaline (ADR) and vasopressin (VAS) are used as vasopressors during cardiopulmonary resuscitation. Data regarding their effects on blood-brain barrier (BBB) integrity and neuronal damage are lacking. We hypothesised that VAS given during cardiopulmonary resuscitation (CPR) after haemorrhagic circulatory arrest will preserve BBB integrity better than ADR. METHODS: Twenty-one anaesthetised sexually immature male piglets (with a weight of 24.3 ± 1.3 kg) were bled 35% via femoral artery to a mean arterial blood pressure of 25 mmHg in the period of 15 min. Afterwards, the piglets were subjected to 8 min of untreated ventricular fibrillation followed by 15 min of open-chest CPR. At 9 min of circulatory arrest, piglets received amiodarone 1.0 mg/kg and hypertonic-hyperoncotic solution 4 ml/kg infusions for 20 min. At the same time, VAS 0.4 U/kg was given intravenously to the VAS group (n = 9) while the ADR group received ADR 20 µg/kg (n = 12). Internal defibrillation was attempted from 11 min of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 h after resuscitation. RESULTS: The intracranial pressure (ICP) in the post-resuscitation phase was significantly greater in ADR group than in VAS group. VAS group piglets exhibited a significantly smaller BBB disruption compared with ADR group. Cerebral pressure reactivity index showed that cerebral blood flow autoregulation was also better preserved in VAS group. CONCLUSIONS: Resuscitation with ADR as compared with VAS after haemorrhagic circulatory arrest increased the ICP and impaired cerebrovascular autoregulation more profoundly, as well as exerted an increased BBB disruption though no significant difference in neuronal injury was observed.

Improved neuroprotective effect of methylene blue with hypothermia after porcine cardiac arrest.

BACKGROUND: Induced mild hypothermia and administration of methylene blue (MB) have proved to have neuroprotective effects in cardiopulmonary resuscitation (CPR); however, induction of hypothermia takes time. We set out to determine if MB administered during CPR could add to the histologic neuroprotective effect of hypothermia. METHODS: A piglet model of extended cardiac arrest (12 min of untreated cardiac arrest and 8 min of CPR) was used to assess possible additional neuroprotective effects of MB when administered during CPR before mild therapeutic hypothermia induced 30 min after restoration of spontaneous circulation (ROSC). Three groups were compared: C group (n = 8) received standard CPR; PH group (n = 8) received standard CPR but 30 min after ROSC these piglets were cooled to 34°C; the PH+MB group (n = 8) received an MB infusion 1 min after commencement of CPR and the same cooling protocol as the PH group. Three hours later, the animals were killed. Immediately after death, the brains were harvested pending histological and immunohistological analysis. RESULTS: Circulatory variables were similar in the groups except that cardiac output was greater in the PH+MB group 2-3 h after ROSC. Cerebral cortical neuronal injury and blood-brain barrier disruption was greatest in the C group and least in the MB group. The neuroprotective effect of MB and hypothermia was significantly greater than that of delayed hypothermia alone. CONCLUSION: Administration of MB during CPR added to the short term neuroprotective effects of induced mild hypothermia induced 30 min after ROSC.

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.

Detection and characterisation of renal lesions by multiphasic helical CT.

PURPOSE: The fast helical CT technique allows examination of the kidneys during different phases of contrast medium enhancement. However, every additional phase increases the radiation dosage to the patients. We investigated the detection rate and characterisation of renal lesions during different phases and evaluated them separately, and considered the possibility of excluding phases without loss of important information. MATERIAL AND METHODS: Sixty patients who underwent contrast-enhanced multiphasic renal helical CT examination were included. Every CT phase was evaluated separately. The number of lesions and the characteristics of the lesions were noted and all lesions were viewed together. RESULTS: A total of 153 cysts and 17 solid lesions were detected. The largest and an equal number of cysts (142/143) was detected in the nephrographic and excretory phases. However, the nephrographic phase detected more cortical cysts and the excretory phase detected more sinus cysts. All solid lesions were detected in all phases. Renal parenchymal tumours were best characterised in the cortical phase and angiomyolipomas in the native phase. CONCLUSION: The cortical phase was best for characterisation of renal parenchymal tumours. The nephrographic and excretory phases were best in detecting and characterising renal cysts. The nephrographic phase was the phase giving the least diagnostic information.