Benoît Tavernier

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.

Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach.

Background:Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. Methods:The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. Results:The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86–0.92) for PPV, compared with 0.57 (95% CI: 0.54–0.59) for central venous pressure (P < 10−5). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. Conclusion:Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia.

Heart rate variability during total intravenous anesthesia: Effects of nociception and analgesia

BACKGROUND Changes in heart rate variability (HRV) during anesthesia likely result from the interaction of hypnosis, surgical stimulation, analgesia and direct cardiovascular effects of drugs, but the interaction between these variables is unclear. This study was designed to characterize the impact of both surgical nociception and analgesia on HRV in propofol-anesthetized patients. METHODS HRV was analyzed using wavelet transform in 49 patients (ASA status 1-2) before induction of anesthesia and then throughout stable anesthesia with propofol, in the absence of nociceptive stimulation, and then during surgery, in the presence of deep (adequate) or light (inadequate) analgesia provided by various opioids (sufentanil [n=19], alfentanil [n=18], or remifentanil [n=12]. RESULTS Anesthesia reduced total power as well as high frequency (HF) and low frequency (LF) powers (all: P<0.01), with an increase (P=0.002) in the proportional part of HF power (HFnu). During nociception, HFnu decreased in a sensitive and reproducible way (P<0.01) in case of light analgesia, whereas HRV did not change when patient received adequate analgesia. CONCLUSIONS The nociception-analgesia balance is a direct determinant of HRV during surgical anesthesia. HFnu may behave like an early indicator of inadequate analgesia. These results have potential implication for monitoring adequacy of analgesia in healthy patients undergoing intravenous anesthesia. Additional work is needed for application across patient populations.

Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats

The subcellular mechanisms underlying intrinsic myocardial depression during sepsis remain poorly defined, in particular the relative roles of altered intracellular Ca2+ transients versus changes in myofilament properties. We studied contractile function of cardiac myocytes isolated 12 h after induction of endotoxemia (5 mg/kg intravenous E. coli lipopolysaccharide [LPS]) in conscious rats. Cardiomyocytes from LPS‐injected rats had depressed twitch shortening compared with control cells (4.1±0.2% versus 7.8±0.3%; P<0.001; 0.5‐Hz stimulation), but similar Ca2+ transients (peak indo‐1 ratio 1.13±0.02 versus 1.12±0.02; P = NS). Contractile depression was unaffected by inhibitors of nitric oxide synthase. Steady‐state myofilament response to Ca2+, assessed by tetanization of intact cells over a range of [Ca2+], was reduced significantly in the LPS group (P<0.001). Intracellular pH (SNARF fluorescence) was similar in both groups, but the amount of phosphorylated troponin I present in endotoxemic myocardium was approximatel2y+ twofold greater than in control myocardium. In addition, steady‐state myofilament response to Ca2+ was unaffected by isoproterenol (3 nmol/L) in endotoxemic cells, whereas there was a rightward shift in control cells. A reduction in myofilament response to Ca2+ is the major determinant of intrinsic cardiac depression in systemic endotoxemia. This condition appears to be related to an increase in myocardial troponin I phosphorylation.

Automated pulse pressure and stroke volume variations from radial artery: evaluation during major abdominal surgery

BACKGROUND Off-line calculation of the pulse pressure variation (PPV(ref)) has repeatedly been shown to be a reliable predictor of fluid responsiveness in mechanically ventilated patients. This study was designed to assess the ability of two algorithms for automated calculation of PPV (PPV(auto)) (Intellivue MP 70) and stroke volume variation (SVV(auto)) (FloTrac/Vigileo) to predict fluid responsiveness during abdominal surgery. METHODS We conducted a prospective study of 56 fluid challenges given for haemodynamic instability in 11 patients undergoing major abdominal surgery. Fluid responsiveness was defined as an increase in stroke volume index (SVI) >10%. PPV(ref), PPV(auto), SVV(auto), and SVI (oesophageal Doppler) were recorded simultaneously before and after each fluid challenge. RESULTS PPV(auto) and SVV(auto) both correlated with PPV(ref) [r(corr)=0.87 (P<0.0001) and 0.84 (P<0.0001), respectively; n=77]. All three indices measured before fluid challenges were higher in responder (n=32) than in non-responder (n=24) fluid challenges (P < or = 0.02). The mean areas under the receiver operating characteristic curves were 0.96 (PPV(ref)), 0.96 (PPV(auto)), and 0.95 (SVV(auto)), and the optimal threshold value for each variable was 13%, 13%, and 12%, respectively. All indices correlated with the fluid challenge-induced changes in SVI (PPV(ref): r(corr)=0.65; PPV(auto): r(corr)=0.58; SVV(auto): r(corr)=0.58, P<0.001 for all). CONCLUSIONS PPV(auto) and SVV(auto) predict fluid responsiveness as accurately as off-line PPV(ref) in patients with haemodynamic instability during major abdominal surgery.

Sevoflurane pre- and post-conditioning protect the brain via the mitochondrial KATP channel

BACKGROUND This study aimed to evaluate whether exposure to sevoflurane at the onset of reperfusion provides protection similar to sevoflurane preconditioning and whether the effect depends on mitochondrial potassium ATP-dependent channel (mitoK(ATP)) in a rat model of focal cerebral ischaemia. METHODS Adult Wistar male rats were subjected to focal cerebral ischaemia for 1 h followed by 24 h or 7 days of reperfusion. Preconditioning consisted of 15 min exposure to sevoflurane at 1 minimum alveolar concentration (2.6%) 72 h before ischaemia. Post-conditioning was performed by exposure to sevoflurane immediately at the onset of reperfusion or by a delayed exposure 5 min after the onset of reperfusion. The role of the mitoK(ATP) channel was assessed by i.p. injection of the selective blocker 5-hydroxydecanoate before each sevoflurane administration or by the mitoK(ATP) channel opener, diazoxide (DZX), given in place of sevoflurane. Cerebral infarct size, neurological deficit score, and motor coordination were evaluated 24 h and 7 days after reperfusion. RESULTS Sevoflurane preconditioning and early post-conditioning reduced both cerebral infarct size and neurological defect score at 24 h of reperfusion whereas the sole sevoflurane post-conditioning improved motor coordination. At 7 days, only infarct volume remained lower in pre- and post-conditioned animals. Neuroprotection mediated by sevoflurane was lost when it was given 5 min after the onset of reperfusion and was abolished by inhibition of mitoK(ATP). DZX alone mimicked sevoflurane-induced pre- and post-conditioning. CONCLUSIONS The pretreatment with sevoflurane or its early administration at reperfusion provides neuroprotection via mitoK(ATP) in a rat model of focal cerebral ischaemia.

Can Changes in Arterial Pressure be Used to Detect Changes in Cardiac Output during Volume Expansion in the Perioperative Period

Background:Cardiac output (CO) is rarely monitored during surgery, and arterial pressure remains the only hemodynamic parameter for assessing the effects of volume expansion (VE). However, whether VE-induced changes in arterial pressure accurately reflect changes in CO has not been demonstrated. The authors studied the ability of VE-induced changes in arterial pressure and in pulse pressure variation to detect changes in CO induced by VE in the perioperative period. Methods:The authors studied 402 patients in four centers. Hemodynamic variables were recorded before and after VE. Response to VE was defined as more than 15% increase in CO. The ability of VE-induced changes in arterial pressure to detect changes in CO was assessed using a gray zone approach. Results:VE increased CO of more than 15% in 205 patients (51%). Areas under the receiver operating characteristic curves for VE-induced changes in systolic, diastolic, means, and pulse pressure ranged between 0.64 and 0.70, and sensitivity and specificity ranged between 52 and 79%. For these four arterial pressure–derived parameters, large gray zones were found, and more than 60% of the patients lay within this inconclusive zone. A VE-induced decrease in pulse pressure variation of 3% or more allowed detecting a fluid-induced increase in CO of more than 15% with a sensitivity of 90% and a specificity of 77% and a gray zone between 2.2 and 4.7% decrease in pulse pressure variation including 14% of the patients. Conclusion:Only changes in pulse pressure variation accurately detect VE-induced changes in CO and have a potential clinical applicability.

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.

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.

Liver transplantation without the use of fresh frozen plasma.

In orthotopic liver transplantations (OLT), fresh frozen plasma (FFP) is classically used to normalize coagulation factor concentrations.In this study, 28 OLT were performed without the use of FFP. According to their preoperative factor V (FV) levels, two groups of patients were defined: Group 1 (13 patients, FV >10% and <60%) and Group 2 (15 patients, FV >60%). Spontaneous evolution of coagulation factors, concentration, and bleeding were observed during OLT and up to 48 h after surgery. Total intraoperative bleeding was similar in both groups (3460 +/- 2700 mL and 3470 +/- 2110 mL in Groups 1 and 2, respectively). Levels of clotting factors were not different between groups after the anhepatic stage. The lowest values were noted after reperfusion. Thirty-six hours after surgery, all levels of clotting factors in both groups were more than 50%, with FV level increasing the most rapidly. Hematocrit from the subhepatic drainage liquid was 1.8% and less than 1% at 24 and 48 h, respectively, after surgery. No reintervention for bleeding was necessary. These results suggest that, in OLT, correct hemostasis can be assumed without FFP use when hyperfibrinolysis, platelet count, fibrinogen rate, and hemodynamic status are controlled. (Anesth Analg 1996;83:681-6)