Gilles Lebuffe

Systolic Pressure Variation as a Guide to Fluid Therapy in Patients with Sepsis-induced Hypotension

Background Monitoring left ventricular preload is critical to achieve adequate fluid resuscitation in patients with hypotension and sepsis. This prospective study tested the correlation of the pulmonary artery occlusion pressure, the left ventricular end‐diastolic area index measured by transesophageal echocardiography, the arterial systolic pressure variation (the difference between maximal and minimal systolic blood pressure values during one mechanical breath), and its delta down (dDown) component (= apneic ‐ minimum systolic blood pressure) with the response of cardiac output to volume expansion during sepsis. Methods Preload parameters were measured at baseline and during graded volume expansion (increments of 500 ml) in 15 patients with sepsis‐induced hypotension who required mechanical ventilation. Each volume‐loading step (VLS) was classified as a responder (increase in stroke volume index >or= to 15%) or a nonresponder. Successive VLSs were performed until a nonresponder VLS was obtained. Results Thirty‐five VLSs (21 responders) were performed. Fluid loading caused an overall significant increase in pulmonary artery occlusion pressure and end‐diastolic area index, and a significant decrease in systolic pressure variation and delta down (P < 0.01). There was a significant difference between responder and nonresponder VLSs in end‐diastolic area index, systolic pressure variation, and dDown, but not in pulmonary artery occlusion pressure. Receiver‐operator curve analysis showed that dDown was a more accurate indicator of the response of stroke volume index to volume loading than end‐diastolic area index and pulmonary artery occlusion pressure. A dDown component of more than 5 mmHg indicated that the stroke volume index would increase in response to a subsequent fluid challenge (positive and negative predictive values: 95% and 93%, respectively). Conclusion The dDown component of the systolic pressure variation is a sensitive indicator of the response of cardiac output to volume infusion in patient with sepsis‐induced hypotension who require mechanical ventilation.

Hepatic venous pressure gradient in the assessment of portal hypertension before liver resection in patients with cirrhosis

Preoperative measurement of hepatic venous pressure gradient (HVPG) is not performed routinely before hepatectomy in patients with cirrhosis, although it has been suggested to be useful. This study investigated whether preoperative HVPG values and indirect criteria of portal hypertension (PHT) predict the postoperative course in these patients.

Effects of hybrid minimally invasive oesophagectomy on major postoperative pulmonary complications

Morbidity after oesophageal cancer surgery remains high, mainly due to major postoperative pulmonary complications (MPPCs). The aim of this study was to test the hypothesis that hybrid minimally invasive oesophagectomy (HMIO) decreases the 30‐day MPPC rate without compromising oncological outcomes.

Brain ischemic preconditioning is abolished by antioxidant drugs but does not up-regulate superoxide dismutase and glutathion peroxidase

The present work examined the hypothesis that brain ischemic tolerance induced by ischemic preconditioning (IPC) is triggered by an initial oxidative stress and is associated with an increase in antioxidant enzyme activities as one end-effector of the neuroprotection. Wistar rats were preconditioned by a single 3-min occlusion of the middle cerebral artery. After a various duration of reperfusion (30 min, 24, 72 or 168 h), rats were subjected to a 60-min focal ischemia and sacrificed 24 h later. Cerebral infarcts were significantly reduced when performed during the 24- to 72-h time window after IPC. The pretreatment with the protein synthesis inhibitor, cycloheximide (1 mg/kg, i.p., 30 min prior to IPC), completely suppressed the neuroprotection. The free radical scavenger, dimethylthiourea (DMTU; 300 mg/kg, i.p., 30 min prior to IPC) and the antioxidant ebselen (10 mg/kg, oral cramming, 2 h before and 12 h after IPC) also abolished the IPC-induced protection of the brain. Nevertheless, IPC did not induce any delayed changes in antioxidant enzyme (superoxide dismutase, glutathion peroxidase) activities nor in the neuronal expression of Mn and Cu/Zn superoxide dismutase. These results indicate that an initial oxidative stress could be involved as a trigger of IPC, while antioxidant enzymes do not play a key role as end-effectors in such a neuroprotection.

Regional capnometry with air-automated tonometry detects circulatory failure earlier than conventional hemodynamics after cardiac surgery.

UNLABELLED Gastrointestinal automated online air tonometry has been proposed for monitoring gastric perfusion in patients at risk of circulatory failure (CF) after cardiopulmonary bypass. In this study, CF was prospectively defined as the requirement for vasoactive support to maintain mean arterial pressure > or = 70 mm Hg after optimization of preload. Hemodynamic variables--oxygen (O2) delivery (DO2), O2 uptake (Vo2), venous-to-arterial [P(v-a)CO2], gastric-to-arterial [P(r-a)CO2], and gastric-to-end-tidal [P(r-et)CO2]Pco2 gap-were retrospectively compared in 14 patients with or without CF during a 12-hr postbypass period (HO-H12). In contrast to patients without CF (n = 7), in patients with CF (n = 7) increased VO2 was not associated with an increase in DO2. P(r-a)CO2 was larger at H0 in CF patients and was the only variable that differed between the two groups. P(v-a)CO2 did not vary significantly in both groups, whereas P(r-a)CO2 increased to a larger extent from H0 to H12 in patients with CF, suggesting selective gastrointestinal hypoperfusion in this group. P(r-et)CO2 provided comparable information to P(r-a)CO2. Hospital length of stay was 4 days longer (P < 0.05) in patients with CF. Increased P(r-a)CO2 and P(r-et)CO2, as monitored with automated air tonometry, were associated with rapid occurrence of CF and prolonged hospital stay after cardiac surgery. IMPLICATIONS Regional and automated capnometry may be used noninvasively to identify patients at risk of circulatory failure after cardiopulmonary bypass earlier than with conventional variables.

Gabapentin attenuates late but not early postoperative pain after thyroidectomy with superficial cervical plexus block.

BACKGROUND: Preoperative oral gabapentin has been shown to reduce postoperative pain. However, the effects of gabapentin as an adjunct to regional anesthesia is unclear and its effects on chronic pain remains unknown. In patients undergoing thyroidectomy, we investigated the effects on early and late (at 6 mo) postoperative pain of preoperative oral gabapentin as an adjunct to superficial cervical plexus block (SCPB). METHOD: Fifty consecutive consenting patients were randomized to receive either 1200 mg of gabapentin (Group G) or placebo (Group P) 2 h preoperatively. Preoperative anxiety was assessed on a numeric scale from 0 to 6. A SCPB was performed after a standardized induction of anesthesia. The primary outcome, analgesic drug consumption, was assessed during the procedure and postoperatively in the postanesthesia care unit and after discharge to the ward. Over the first 24 h, pain levels at rest and during swallowing were measured on a numeric scale from 0 to 10. If the pain level was more than 4/10 at rest, patients received 1 g/6 h of IV paracetamol and/or 50 mg/6 h of IV tramadol as a rescue analgesic treatment in the interval. The day before operation and 6 mo after thyroidectomy, included patients were asked to answer a neuropathic pain diagnostic questionnaire. RESULTS: Population characteristics, preoperative anxiety, intraoperative drug consumption, procedure duration, and postoperative care unit stay were comparable in both groups. Analgesic consumption during the first 24 postoperative hours was similar in both groups (G: 3 [0–5] doses/24 h; P: 3 [1–5] doses/24 h; P = NS), as well as pain at rest (G: 2,2 [0.2–3.7]; P: 2 [0–6.3]; P = NS), and during swallowing (G: 2.8 [0.4–8.9]; P: 3 [1.4–6.3]; P = NS]). Eight patients had a diagnostic questionnaire score more than 3, 6 mo after operation versus 2 in preoperative period (P = 0.04). Such delayed neuropathic pain complaints were reported in seven patients receiving SCPB alone and only in one patient receiving both SCPB and preoperative adjunctive oral gabapentin. (P = 0.01). CONCLUSION: Oral preoperative administration of gabapentin did not modify immediate pain management in thyroidectomy patients receiving SCPB, but prevented delayed neuropathic pain at 6 mo.

Postconditioning in focal cerebral ischemia: Role of the mitochondrial ATP-dependent potassium channel

INTRODUCTION Ischemic postconditioning (IpostC) has been described in both heart and brain. The first aim of this study was to evaluate the effects of IpostC on brain infarct size and neurological function in the middle cerebral artery occlusion (MCAO) model. The second aim was to determine the involvement of the mitochondrial potassium ATP-dependent channel (mitoK(ATP)) opening and its capacity to improve mitochondrial dysfunction induced by ischemia-reperfusion. METHODS Wistar rats were subjected to 60min MCAO followed by 24-h reperfusion. Postconditioning was performed by 3 cycles of 30-s occlusion-reperfusion at the onset of reperfusion. Three behavioral tests were performed following 24h of reperfusion. Involvement of mitoK(ATP) was determined by the modulation of IpostC effects by 5-hydroxydecanoate (5-HD) and diazoxide. Mitochondrial function after 24h of reperfusion on isolated mitochondria was assessed through mitochondrial oxygen consumption, mitochondrial membrane potential and calcium retention capacity to evaluate impact of IpostC on mitochondrial permeability transition pore (MPTP) opening. RESULTS IpostC resulted in a 40% decrease in infarct size and improved neurological outcome. These effects were lost when IpostC was delayed by 5min. The administration of diazoxide resulted in a 60% in infarct size. The beneficial effects of IpostC and diazoxide were blocked by 5-HD. Furthermore, 5-HD also blocked the inhibition of MPTP opening by IpostC and diazoxide. The hyperpolarization induced by ischemia-reperfusion was corrected by IpostC without any effect on oxidative phosphorylation. CONCLUSION Our results confirm ischemic postconditioning-induced neuroprotection. They also support the involvement of mitoK(ATP) opening and its role in inhibiting the opening of MTPT induced by postconditioning.

Venous Oxygen Saturation as a Physiologic Transfusion Trigger

This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/yearbook. Further information about the Yearbook of Intensive Care and Emergency Medicine is available from http://www.springer.com/series/2855.

Preconditioning by an in situ administration of hydrogen peroxide: Involvement of reactive oxygen species and mitochondrial ATP-dependent potassium channel in a cerebral ischemia–reperfusion model

Reactive oxygen species (ROS) and the mitochondrial ATP-dependent potassium channel (mitoK(+)(-)(ATP)) play a major role in myocardial preconditioning. The same pathways seem to be involved in cerebral preconditioning. The aim of this study was to evaluate ROS involvement during the initial phase of delayed preconditioning and its relationship with mitoK(+)(-ATP) opening in a rat model of cerebral ischemia-reperfusion. Ischemia was induced by a 1-h occlusion of middle cerebral artery followed by a 24-h reperfusion period. A delayed preconditioning was induced by a 3-min ischemia (IPC), an in situ infusion of hydrogen peroxide (H(2)O(2)), or an administration of mitoK(+)(-ATP) agonist diazoxide, 72 h before the ischemia-reperfusion (I/R). IPC was performed in the presence or not of N-acetyl-cysteine (NAC) or 5-hydroxydecanoate (5-HD). A neuroprotection was induced by IPC and administration of H(2)O(2) or diazoxide. The decrease in infarct size was respectively 24.5%, 45.7% and 24.6%. IPC was abolished by 5-HD and NAC, indicating that mitoK(+)(-ATP) and ROS are involved. The protection induced by H(2)O(2) was blocked by 5-HD and diazoxide triggering was abolished by NAC. This strong relationship between ROS and mitoK(+)(-ATP) needs to be clarified as ROS might be involved both upstream and downstream of mitoK(+)(-ATP) opening.

Clinical relevance of data from the pulmonary artery catheter

The usefulness of parameters measured using the pulmonary artery catheter has been challenged because no benefit in patient outcome has been observed in clinical trials. However, technological advances have been made, including continuous measurement of cardiac output (CO), mixed venous saturation (SvO2), and right ventricle end-diastolic volume (CEDV) have been made. Pulmonary artery occlusion pressure (PAOP), CEDV and right atrial pressure (RAP) are not good predictors of fluid load responsiveness except when very low. Despite this methodological limitation, variation of these parameters during fluid loading remains a good indicator of fluid challenge tolerance. Accuracy of continuous thermodilution and SvO2 measurement has been demonstrated in vitro and at bedside. A decrease in SvO2 is a global index of an inadequate oxygen delivery (DO2)/oxygen requirement relationship. In this setting, a therapeutic decision to improve determinants of SvO2 should be considered with the help of all other PAC parameters. Technological improvement transforms PAC in a real time integrated physiological device and allows one to observe the impact of therapeutic intervention. What we need now is a clinical trial with a PAC-guided treatment algorithm taking into account the above integrated PAC parameters.