Alteration of muscle membrane excitability in sepsis: possible involvement of ciliary nervous trophic factor (CNTF).

One of the main factor involved neuromyopathy acquired in intensive care unit (ICU) appears to be sepsis. It induces the release of many pro- and anti-inflammatory factors which can directly modulate the muscle excitability. We have studied the effects of one of them: the ciliary nervous trophic factor (CNTF) which is a cytokine released in the early phase of sepsis. CNTF induces a decrease in the sodium current and an increase in resting potential as in sodium inversion potential. These effects could participate to the hypo-excitability observed during sepsis and could be involved in the ICU acquired neuromyopathy. As for TNFα, this early effect is mainly mediated by protein kinase C (PKC) activation and appears to be a reversible post-transcriptional effect.

Tumor necrosis factor-α downregulates sodium current in skeletal muscle by protein kinase C activation: involvement in critical illness polyneuromyopathy.

Sepsis is involved in the decrease of membrane excitability of skeletal muscle, leading to polyneuromyopathy. This effect is mediated by alterations of the properties of voltage-gated sodium channels (Na(V)), but the exact mechanism is still unknown. The aim of the present study was to check whether tumor necrosis factor (TNF-α), a cytokine released during sepsis, exerts a rapid effect on Na(V). Sodium current (I(Na)) was recorded by macropatch clamp in skeletal muscle fibers isolated from rat peroneus longus muscle, in control conditions and after TNF-α addition. Analyses of dose-effect and time-effect relationships were carried out. Effect of chelerythrine, a PKC inhibitor, was also studied to determine the way of action of TNF-α. TNF-α induced a reversible dose- and time-dependent inhibition of I(Na). A maximum inhibition of 75% of the control current was observed. A shift toward more negative potentials of activation and inactivation curves of I(Na) was also noticed. These effects were prevented by chelerythrine pretreatment. TNF-α is a cytokine released in the early stages of sepsis. Besides a possible transcriptional role, i.e., modification of the channel type and/or number, we demonstrated the existence of a rapid, posttranscriptional inhibition of Na(V) by TNF-α. The downregulation of the sodium current could be mediated by a PKC-induced phosphorylation of the sodium channel, thus leading to a significant decrease in muscle excitability.

TNFα increases resting potential in isolated fibres from rat peroneus longus by a PKC mediated mechanism: involvement in ICU acquired polyneuromyopathy.

BACKGROUND AND AIMS: Our aim was to investigate the effect of TNFα on muscle resting potential (RP) and then in muscle excitability and to demonstrate another mechanism implicated in intensive care units (ICU) acquired polyneuromyopathy. METHODS: Experiments were carried out on adult female Wistar rats. After isolation of muscle fibres from peroneus longus, influence of TNFα was tested on RP by using intracellular microelectrodes. Digoxin and chelerythrin were used to determine the mechanism of TNFα action. RESULTS: First, we found that TNFα induced a concentration dependent increase of muscle RP and that this mechanism, which was blocked by digoxin, was due to an effect on the Na/K ATPase. As it was also blocked by chelerythrin it was concluded that this effect was mediated by PKC activation of the Na/K ATPase. CONCLUSIONS: We demonstrated that TNFα leads to a PKC mediated increase in muscle RP. Depolarization needed to reach the threshold voltage for muscle action potential should then be higher and this could be involved in the decrease in muscle excitability observed in acquired polyneuromyopathy.

The accuracy of noninvasive hemoglobin measurement by multiwavelength pulse oximetry after cardiac surgery.

BACKGROUND: In March 2008, a new multiwavelength pulse oximeter, the Radical 7 (Rad7; Masimo Corp., Irvine, CA), was developed that offers noninvasive measurement of hemoglobin concentration. Accuracy has been established in healthy adults and some surgical patients, but not in cardiac surgery intensive care patients, a group at high risk of postoperative bleeding events and anemia in whom early diagnosis could improve management. METHODS: In this prospective, observational study conducted in a cardiovascular intensive care unit, we compared hemoglobin concentrations shown by the Rad7 with arterial hemoglobin concentrations determined by an automated hematology analyzer, XE-2100 (Roche, Neuilly sur Seine, France). Two software versions of Rad7 (V 7.3.0.1 [42 points of comparison in 14 patients] and the updated V 7.3.1.1 [61 points of comparison in 27 patients]) were studied during two 1-week periods. Bias, defined as the difference between the 2 methods (Masimo SpHb-XE-2100 laboratory hemoglobin), was calculated. A negative bias indicated that the Masimo underestimated hemoglobin compared with the laboratory analyzer. Correlation between the perfusion index given by Rad7 and the hemoglobin bias was also studied. RESULTS: Correlations between Rad7 and XE-2100 were weak for both software versions (R2=0.11 for V 7.3.0.1 and R2=0.27 for V 7.3.1.1). Mean bias was -1.3 g/dL for V 7.3.0.1 and -1.7 g/dL for V 7.3.1.1, with wide 95% prediction intervals for the bias (respectively, -4.6 to 2.1 g/dL and -5.7 to 2.3 g/dL). The absolute hemoglobin bias tended to increase when the perfusion index decreased. For the V 7.3.0.1 software, the average absolute bias was 1.9 g/dL for perfusion index<2 and 0.8 g/dL for perfusion index>2 (P=0.03). For V 7.3.1.1, the mean absolute bias was 2.1 g/dL when the perfusion index was <2, and 1.6 g/dL when the perfusion index was >2 (P=0.26). CONCLUSIONS: Our study demonstrates poor correlation between hemoglobin measured noninvasively by multiwavelength pulse oximetry and a laboratory hematology analyzer. The difference was greater when the pulse oximetry perfusion index was low, as may occur in shock, hypothermia, or vasoconstriction patients. The multiwavelength pulse oximetry is not sufficiently accurate for clinical use in a cardiovascular intensive care unit.

Acute kidney injury after aneurysmal subarachnoid hemorrhage: is chloride really responsible?

Sadan et al. find an association between acute kidney injury and high chloride containing a hypertonic solution. Recent large prospective non-randomized studies bring conflicting results on the relationship between chloride and acute kidney injury. We discuss Sadan et al.'s results according to the recent literature.

Acute renal dysfunction after cardiac surgery with cardiopulmonary bypass is associated with plasmatic IL6 increase.

BACKGROUND: Acute renal dysfunction (ARD) is common after cardiac surgery with cardiopulmonary bypass (CPB). CPB results in a sudden systemic inflammatory response. Systemic and local pro-inflammatory cytokines synthesis has been linked with sub-clinical renal injury, especially tubular lesions. Therefore, we sought to assess the systemic synthesis pro-inflammatory cytokines and its association with perioperative ARD after cardiac surgery with CPB. METHODS: Sixty-two patients undergoing cardiac surgery with CPB were prospectively included. Four groups of patients were defined according to blood creatinine increase: no ARD (less than 25% increase), faint ARD (25-50% increase), moderate ARD (50-100% increase), severe ARD (more than 100% increase). RESULTS: Within the 48 post-operative hours was ARD observed as no dysfunction (41.9%), faint (32.2%), moderate (16.1%), severe (9.6%). One patient had to undergo a dialysis. Pre-operative characteristics were homogenous between the four groups excepted the left ventricle ejection fraction. ARD was associated with a low urinary output with high sodium excretion fraction. Significant increase of IL-6 level occurred when patients underwent a severe ARD despite no significant differences for the CRP and TNF-alpha concentrations. CONCLUSION: Severe acute renal dysfunction after cardiac surgery with CPB is associated with a significant increased IL-6 systemic production.

The reproducibility of Stewart parameters for acid-base diagnosis using two central laboratory analyzers.

BACKGROUND: Acid-base derangements can be interpreted using the Stewart-Fencl approach, which includes calculation of the apparent strong ion difference (SID(app)), the effective SID (SID(eff)), and the strong ion gap (SIG). These calculations require the measurement of several variables. We hypothesized that the SID and SIG calculated by different analyzers would not be reproducible because of variability in the measured values. METHODS: In this prospective observational study conducted in a biochemistry laboratory, we analyzed 179 routine blood samples from consecutive patients over a 3-mo period using two automated blood chemistry analyzers, the LX20 (Beckman) and the Modular (Roche). Measured and calculated parameters from the two analyzers were compared. RESULTS: Although the correlation between measured values was satisfactory, there were large differences in the limits of agreement for calculated values (SID(app): 9.6 mEq/L, SID(eff): 6.4 mEq/L, and SIG: 11.7 mEq/L) and a weak correlation (SID(app): r(2) = 0.54 and SIG: r(2) = 0.12) between the analyzers. CONCLUSIONS: The results of the Stewart-Fencl approach for interpretation of acid-base status can vary according to the analyzer used. These differences may have important clinical and research implications..

Effects of chronic sepsis on contractile properties of fast twitch muscle in an experimental model of critical illness neuromyopathy in the rat.

OBJECTIVE: Critical illness polyneuromyopathy has been extensively studied in various animal models regarding electrophysiological aspects or molecular mechanisms involved in its physiopathology; however, little data are available on its main clinical feature, that is, muscular weakness. We have studied the effects of chronic sepsis in rats with special consideration to contractile and neuromuscular blockade properties in relation with the level of messenger RNA (mRNA) coding for ryanodine and acetylcholine receptors. DESIGN: This was an experimental animal study. SETTING: This study was conducted at a university laboratory. SUBJECTS: Subjects consisted of Wistar rats. INTERVENTIONS: Chronic sepsis was achieved by cecal ligation and needle perforation. Ten days after surgery, fast twitch extensor digitorum longus was excised for extraction and assays of mRNA coding for ryanodine and acetylcholine receptor subunits and contralateral muscle was tested in vivo on a mechanical bench. A fatigability index was measured and neuromuscular blockade properties using atracurium were evaluated. MEASUREMENTS AND MAIN RESULTS: A decrease in active force developed by extensor digitorum longus associated with an increase in passive force is induced by chronic sepsis. Maximal force at optimal length during twitch contraction was significantly reduced (0.25 +/- 0.09 N vs. 0.17 +/- 0.06 N); contraction and relaxation speeds were higher as shown by the decrease of respective time constants (3.75 +/- 0.01 msec vs. 2.70 +/- 0.0 msec, 10.76 +/- 0.03 msec vs. 7.62 +/- 0.03 msec) in the control group compared with the septic group. Fatigability index was significantly lower (23 +/- 0.11% vs. 59 +/- 0.19%) in septic rats. These rats also showed quicker blockade and shorter recovery after atracurium administration. Sepsis induced a significant increase of the expression of ryanodine receptor (RyR) RyR1 along with a steady expression of RyR3 mRNA, leading to a 5.6-fold increase of RyR1/RyR3 ratio with a steadiness of mRNA corresponding to acetylcholine-receptors. CONCLUSIONS: Chronic inflammation and sepsis induced a decrease in contractile performances of extensor digitorum longus along with accelerated kinetics of atracurium possibly induced by modified expression of RyR1 receptors and not acetylcholine-receptors.

Sudden death after major head and neck surgery.

PURPOSE OF REVIEW: This review will discuss the mortality after major ear, nose and throat surgery, particularly sudden death. It will also discuss the postoperative follow-up of patients. RECENT FINDINGS: Sudden death is a rare event after major ear, nose and throat surgery, and occurs mainly during the first three postoperative days. SUMMARY: In more recent studies, the mortality rate after neck dissection was below 4%, which is at a lower value than reported in previous studies. Sudden deaths have been described, however, mainly during the first three postoperative days. Alcoholism and perioperative hypotension are two predictive factors for cardiac complications. Careful follow-up of these patients during the early postoperative period should be performed to reduce the mortality by shortening the delay of care.