Non-invasive assessment of fluid responsiveness using CNAP™ technology is interchangeable with invasive arterial measurements during major open abdominal surgery.

BACKGROUND: Dynamic variables of fluid responsiveness (FR), such as pulse pressure variation (PPV), have been shown to predict the response to a fluid challenge accurately. A recently introduced non-invasive technology based on the volume-clamp method (CNAP™) offers the ability to measure PPV continuously (PPVCNAP). However, the accuracy regarding the prediction of FR in the operating room has to be proved. METHODS: We compared PPVCNAP with an invasive approach measuring PPV using the PiCCO technology (PPVPiCCO). We studied 47 patients undergoing major open abdominal surgery before and after a passive leg-raising manoeuvre and i.v. fluid resuscitation. A positive response to a volume challenge was defined as ≥15% increase in stroke volume index obtained with transpulmonary thermodilution. Bootstrap methodology was used with the grey zone approach to determine the area of inconsistency regarding the ability of PPVPiCCO and PPVCNAP to predict FR. RESULTS: In response to the passive leg-raising manoeuvre, PPVPiCCO predicted FR with a sensitivity of 81% and a specificity of 72% [area under the curve (AUC) 0.86] compared with a sensitivity of 76% and a specificity of 72% (AUC 0.78) for PPVCNAP Regarding the volume challenge in the operating room, PPVPiCCO predicted FR with a sensitivity of 87% and a specificity of 100% (AUC 0.97) compared with a sensitivity of 91% and specificity of 93% (AUC 0.97) for PPVCNAP The grey zone approach identified a range of PPVPiCCO values (11-13%) and PPVCNAP values (7-11%) for which FR could not be predicted reliably. CONCLUSIONS: Non-invasive assessment of FR using PPVCNAP seems to be interchangeable with PPVPiCCO in patients undergoing major open abdominal surgery. CLINICAL TRIAL REGISTRATION: NCT02166580.

Sufentanil administration guided by surgical pleth index vs standard practice during sevoflurane anaesthesia: a randomized controlled pilot study.

BACKGROUND: Evaluation of analgesia and antinociception during anaesthesia is still a challenging issue and routinely based on indirect and non-specific signs such as movement, tachycardia, or lacrimation. Recently, the surgical pleth index (SPI) derived by finger plethysmography was introduced to detect nociceptive stimulation during anaesthesia. While SPI guidance reduced the number of unwanted events during total i.v. anaesthesia (TIVA), the impact of SPI during volatile-based anaesthesia with intermittent opioid administration has not yet been elucidated. METHODS: Ninety-four patients were randomized into either SPI-guided analgesia or standard practice (Control). In both groups, anaesthesia was maintained with sevoflurane to keep bispectral index values between 40 and 60. In the SPI group, patients received a sufentanil bolus (10 µg) whenever SPI value increased above 50, whereas in the control group, sufentanil was administered according to standard clinical practice. The number of unwanted somatic events, haemodynamics, sufentanil consumption, and recovery times were recorded. RESULTS: The incidence of intraoperative unwanted somatic events was comparable between the groups (P=0.89). No significant differences with respect to hypotensive or hypertensive events were found. The mean (95% confidence interval) sufentanil consumption was non-significantly (P=0.07) reduced in the SPI group, 0.64 (0.57-0.71) vs 0.78 (0.64-0.91) µg min(-1). Recovery times were comparable between the groups. CONCLUSIONS: Sufentanil administration guided by SPI during sevoflurane anaesthesia is clinically feasible. In contrast to TIVA, it did not improve anaesthesia conduct with respect to unwanted somatic events, haemodynamic stability, sufentanil consumption, emergence time, or post-anaesthesia care unit care. Therefore, we conclude that anaesthesia regimen has an impact on beneficial effects by SPI guidance. Clinical trial registration NCT01525537. (Registered at Clinicaltrials.gov.).

Prediction of fluid responsiveness in infants and neonates undergoing congenital heart surgery.

BACKGROUND: Dynamic variables reliably predict fluid responsiveness (FR) in adults, but no data are available regarding their performance in infants. The aim of this prospective study was to assess whether pulse pressure variation (PPV) and stroke volume variation (SVV), in contrast to central venous pressure (CVP) and global end-diastolic volume (GEDV), are applicable in infants undergoing congenital heart surgery and to assess threshold values that may help to guide fluid administration in these patients. METHODS: Twenty-six anaesthetized infants, mean (sd) weight 9.7 (4.3) kg, were studied during closed-chest conditions and changing loading conditions before and after repair of congenital heart disease. Stroke volume index was measured by transoesophageal echocardiography (SVI(TOE)), CVP was measured via a central venous line, GEDV index (GEDVI) was measured by transpulmonary thermodilution, and PPV and SVV were monitored using the PiCCO monitoring system. RESULTS: Fifteen infants had increased SVI(TOE) with fluid loading ≥15% (responders); 11 infants were defined as non-responders. Analysing the relationship between CVP, GEDVI, SVV, and PPV at baseline with volume-induced percentage change in SVI(TOE), only PPV was significantly correlated with ΔSVI(TOE) both before (r=0.54, P=0.004) and after (r=0.73, P>0.0001). As assessed by receiver-operating characteristic curve analysis, only PPV accurately predicted FR before surgical repair [area under the curve (AUC): 0.79, P=0.01] and after surgical repair (AUC: 0.86, P=0.002). CONCLUSIONS: PPV, in contrast to SVV, CVP, and GEDVI, predicted FR in infants undergoing congenital heart surgery both before and after repair of congenital heart disease.

A comparison of the Nexfin® and transcardiopulmonary thermodilution to estimate cardiac output during coronary artery surgery.

The newly introduced Nexfin(®) device allows analysis of the blood pressure trace produced by a non-invasive finger cuff. We compared the cardiac output derived from the Nexfin and PiCCO, using transcardiopulmonary thermodilution, during cardiac surgery. Forty patients with preserved left ventricular function undergoing elective coronary artery bypass graft surgery were studied after induction of general anaesthesia and until discharge to the intensive care unit. There was a significant correlation between Nexfin and PiCCO before (r(2) = 0.81, p < 0.001) and after (r(2) = 0.56, p < 0.001) cardiopulmonary bypass. Bland-Altman analysis demonstrated the mean bias of Nexfin to be -0.1 (95% limits of agreement -0.6 to +0.5, percentage error 23%) and -0.1 (-0.8 to +0.6, 26%) l.min(-1).m(-2), before and after cardiopulmonary bypass, respectively. After a passive leg-raise was performed, there was also good correlation between the two methods, both before (r(2) = 0.72, p < 0.001) and after (r(2) = 0.76, p < 0.001) cardiopulmonary bypass. We conclude that the Nexfin is a reliable method of measuring cardiac output during and after cardiac surgery.

Accuracy of the pleth variability index to predict fluid responsiveness depends on the perfusion index.

BACKGROUND: Respiratory variations in plethysmographic waveform amplitudes derived from pulse oximetry are believed to predict fluid responsiveness. The non-invasive pleth variability index (PVI) is a variable based on the calculation of changes in the perfusion index (PI). The aim of the following study was to examine whether the predictive power of PVI depends on different values of PI. METHODS: Eighty-one patients undergoing elective coronary artery surgery were studied before operation: at baseline after induction of anaesthesia and during passive leg raising (PLR). Each patient was monitored with central venous pressure (CVP), the PiCCO monitor and the non-invasive Masimo monitoring system. Stroke volume index by transpulmonary thermodilution (SVI(TPTD)), pulse pressure variation (PPV), stroke volume variation (SVV) and systemic vascular resistance index (SVRI) were measured using the PiCCO monitoring system. PI and PVI were obtained by pulse oximetry. RESULTS: Responders were defined to increase their SVI(TPTD) >15% after PLR. The highest area under the curve (AUC) was found for PPV (AUC: 0.83, P<0.0001) and SVV (AUC: 0.72, P=0.002), in contrast to PVI (AUC: 0.60, P=0.11) and CVP (AUC: 0.60, P=0.13). The accuracy of PVI to predict fluid responsiveness was improved on analysing patients with higher PI values. PI of about 4% (n=45) achieved statistical significance (AUC: 0.72, P=0.01). CONCLUSION: The PVI was not able to predict fluid responsiveness with sufficient accuracy. In patients with higher perfusion states, the PVI improved its ability to predict haemodynamic changes, strongly suggesting a relevant influence of the PI on the PVI.

Non-invasive prediction of fluid responsiveness in infants using pleth variability index.

This prospective study assessed whether respiratory variations in velocity time integral, peak blood flow velocity and non-invasive pleth variability index are useful measurements in infants undergoing congenital heart surgery and determined threshold values that may help guide fluid administration. In 27 infants receiving mechanical ventilation, of mean (SD) weight 10.4 (6.3) kg, 13 increased their stroke volume index ≥ 15% following a fluid challenge and 14 did not. The best area under the receiver operating characteristic curve was for the echocardiographic-derived variables respiratory variation in blood peak flow velocity (area under the ROC curve = 0.92; p = 0.0002) and respiratory variation of the velocity time integral (area under the ROC curve = 0.84; p = 0.002). The pleth variability index also predicted fluid responsiveness (area under the ROC curve = 0.79; p = 0.01), in contrast to heart rate (area under the ROC curve = 0.53; p = 0.75) and central venous pressure (area under the ROC curve = 0.57; p = 0.52).

Surgical stress index in response to pacemaker stimulation or atropine.

BACKGROUND: The surgical stress index (SSI) is a new monitoring tool for the assessment of nociception during general anaesthesia. It is calculated based on the heart beat interval and the pulse wave amplitude. Correlation of SSI with nociceptive stimuli and opioid effect-site concentrations has been demonstrated, but the influence of isolated modulation of heart rate (HR) on SSI is still unclear. The aim of this study was to evaluate the effect on SSI of atropine administration and cardiac pacing. METHODS: In 18 anaesthetized ASA III ICU patients, either repetitive cardiac pacemaker stimulation or administration of atropine (10 microg kg(-1)) was performed, and the effect on SSI, arterial pressure, spectral entropy, and bispectral index was analysed. RESULTS: Cardiac pacing at 100 beats min(-1) was followed by an increase in SSI from 26 [17-35 (10-41)] to 59 [53-72 (48-78)] {median [inter-quartile range (range)]} (P=0.0006), whereas other variables remained unaffected. Also, atropine administration increased SSI from 27 [20-34 (16-39)] to 58 [48-70 (41-81)] (P=0.007) without significant effect on other variables except HR. A recalibration of SSI during cardiac pacing leads to a significant decrease in SSI to 49 [40-52 (36-57)] (P=0.03), whereas recalibration after atropine administration had no effect. CONCLUSIONS: SSI values measured in patients receiving atropine or in patients with pacemakers should be interpreted cautiously.

Differences between bispectral index and spectral entropy during xenon anaesthesia: a comparison with propofol anaesthesia.

We enrolled 114 patients, aged 65-83 years, undergoing elective surgery (duration > 2h) into a randomised, controlled study to evaluate the performance of bispectral index and spectral entropy for monitoring depth of xenon versus propofol anaesthesia. In the propofol group, bispectral index and state entropy values were comparable. In the xenon group, bispectral index values resembled those in the propofol group, but spectral entropy levels were significantly lower. Mean arterial blood pressure was higher and heart rate was lower in the xenon group than in the propofol group. Bispectral index and spectral entropy considerably diverged during xenon but not during propofol anaesthesia. We therefore conclude that these measures are not interchangeable for the assessment of depth of hypnosis and that bispectral index is likely to reflect actual depth of anaesthesia more precisely compared with spectral entropy.

Neurotoxicity of deoxycoformycin: effect of constant infusion on adenosine deaminase, adenosine, 2'-deoxyadenosine and monoamines in the mouse brain.

The tight-binding adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF), was continuously infused into mice by intraperitoneal implantation of microosmotic pumps delivering the compound at a rate of 0.16 mg hr-1 kg-1 for up to 6 days. The activity of cerebral adenosine deaminase was nearly totally inhibited. The amount of adenosine and 2'-deoxyadenosine was determined in the brain frozen in liquid nitrogen through the intact skull bone. The concentration of adenosine was about 1 nmol/g, and was essentially not altered following treatment with deoxycoformycin. Deoxycoformycin induced a progressive increase in cerebral content of 2'-deoxyadenosine, which after 1 day of treatment equalled the amount of adenosine. The concentrations of serotonin, dopamine and noradrenaline in the brain were not altered.

5-HT depletion with 5,7-DHT, PCA and PCPA in mice: differential effects on the sensitivity to 5-MeODMT, 8-OH-DPAT and 5-HTP as measured by two nociceptive tests.

Depletion of 5-hydroxytryptamine (5-HT) in mice was produced by intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT, 80 micrograms) or by systemic injections of p-chloroamphetamine (PCA, 3 X 40 or 4 X 40 mg/kg), p-chlorophenylalanine (PCPA, 5 X 400 or 14 X 400 mg/kg) or combined PCA (3 X 40 mg/kg) + PCPA (11 X 400 mg/kg). Neither of the pretreatments altered nociception in the increasing temperature hot-plate test, whereas hyperalgesia was demonstrated in 5,7-DHT lesioned animals in the tail-flick test. 5,7-DHT-pretreatment enhanced the antinociceptive effect of the 5-HT agonists 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-hydroxytryptophan (5-HTP). This effect was observed after 2, 5 and 8 days in the tail-flick test and after 5 and 8 days in the hot-plate test. However, pretreatment with PCPA or PCA failed to alter the antinociception elicited by the 5-HT agonists, although a tendency towards enhancement of antinociception was found after combined treatment with PCA and PCPA. It is suggested that the injection of 5,7-DHT induces denervation supersensitivity of post-synaptic 5-HT receptors. The lack of such supersensitivity after PCPA-pretreatment which induces similar 5-HT depletion to 5,7-DHT, may suggest that other factors than the absence of 5-HT may contribute to the development of denervation supersensitivity. Alternatively, the three 5-HT depleting agents may produce a qualitatively different reduction of 5-HT.

Effect of probenecid on endogenous and exogenous 3,4-dihydroxyphenylacetic acid and homovanillic acid in the rat brain.

The two dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured in corpus striatum and hippocampus in rats after an intracerebroventricular injection of DOPAC or HVA. Probenecid 200 mg/kg i.p. increased the concentration of HVA by the same factor in both control animals and animals treated with HVA. Probenecid had no effect on the DOPAC concentration in control animals or in animals treated with DOPAC. After DOPAC intraventricularly some increase in the HVA concentration could be seen. Pargyline 75 mg/kg was given i.m. and the decline of HVA and DOPAC in corpus striatum was compared in animals with or without probenecid treatment (200 mg/kg i.p.). In the control animals DOPAC declined more rapidly than did HVA. In the probenecid-treated animals there was no change in the DOPAC curve while the HVA showed a slower elimination but still with an exponential curve. The conclusion is drawn that there is an active mechanism for the excretion of DOPAC which is not identical with the excretion mechanism for HVA. A considerable part of the dopamine is directly deaminated to DOPAC in vivo and some of this DOPAC is probably O-methylated to HVA.

Involvement of central serotonergic pathways in nefopam-induced antinociception.

The possible involvement of central serotonergic pathways in the mechanism of action of nefopam was investigated in male albino mice. Nefopam (15 mg/kg i.p.) did not alter the concentration of serotonin or its metabolite 5-hydroxyindole acetic acid in frontal cortex or spinal cord. Lesions of the ascending serotonergic pathways were made by systemic administration of p-chloroamphetamine (PCA). Serotonin depletion in all serotonergic systems was obtained by means of p-chlorophenylalanine (PCPA). Two different nociceptive assays were used, the formalin test and the increasing temperature hot plate test. PCPA pretreatment significantly reduced the effect of nefopam (15 mg/kg) in the formalin test. In contrast, nefopam-induced analgesia was not affected by PCA pretreatment, either in the formalin test or in the increasing temperature hot plate test. In conclusion, the data suggest that descending serotonergic pathways are involved in nefopam-induced antinociception.

Pharmacological manipulation with the descending serotonergic system or transection of the mouse spinal cord has no effect on ependymal ultrastructure.

In order to investigate an effect of descending nerve fibres on mouse spinal cord ependymal ultrastructure, pharmacological manipulation with the serotonergic system or transection of the spinal cord was done. Biochemical analysis showed an 83% reduction of serotonin content in spinal cord tissue after p-chlorophenylalanine injections and a 93% reduction after transection. However, none of the experimental animals showed changes in ependymal ultrastructure compared to control animals as revealed by electron microscopy.

Lesions of the ascending serotonergic pathways and antinociceptive effects after systemic administration of p-chloroamphetamine in mice.

The present study reports a method for lesioning of the ascending serotonergic system. The neurotoxic substance p-chloroamphetamine (PCA) was given IP on 2 consecutive days (40 mg/kg/day). After each injection, the animals were kept at 4 degrees C for 4 hr since a lower dose of PCA (25 mg/kg) induced severe hyperthermia. The mortality rate was 12%, considerably lower than previously reported in similar studies. Evaluated 9 days after the last injection of PCA, the uptake of 14C-5-HT into cortical and hippocampal crude synaptosomal preparations was reduced by 50 and 60%, respectively, while the uptake into spinal synaptosomes was unaffected. The uptake of 3H-NA was not significantly altered in any of the structures. Measurements of PCA performed 30 min to 4 hr after IP injections of 5 to 40 mg/kg demonstrated higher concentrations in the cortex than in the lumbar spinal cord. Administration of PCA (5 mg/kg) had an acute antinociceptive effect in the hot-plate and formalin tests, but not in the tail-flick test. Prior treatment with neurotoxic doses of PCA prevented the antinociception but had in itself no effect on the responsiveness in any of the tests. Thus systemic administration of PCA produces highly selective and functional lesions of the ascending serotonergic pathways in mice.

Validation study of Nexfin® continuous non-invasive blood pressure monitoring in critically ill adult patients.

BACKGROUND: Nexfin® (BMEYE, Amsterdam, The Netherlands) is a totally non-invasive blood pressure and cardiac output (CO) monitor based on finger arterial pulse contour analysis. METHODS: We performed an open observational study in a mix of medical-surgical-burns critically ill patients (N.=45) to validate Nexfin obtained blood pressures (MAPnex) against PiCCO (MAPfem) derived blood pressure measurements. MAPnex, MAPfem and corresponding systolic (SBP) and diastolic (DBP) blood pressures were measured continuously and registered with a 2 hour interval during the 8-hour study period. Statistical analysis was performed by Pearson regression, Bland and Altman, Concordance plot and Polar plot analysis. RESULTS: MAPnex shows excellent correlation with MAPfem (R² 0.88, mean bias ± LA -2.3±12.4 mmHg, 14.7% error) and may be used interchangeably with invasive monitoring. The excellent MAPnex -MAPfem correlation was preserved in subgroup analysis for patients with severe hypotension, high systemic vascular resistance, low CO, hypothermia and in patients supported by inotropic/vasopressive agents. MAPnex is able to follow changes in MAPfem during the same time interval (level of concordance 85.5%). Nexfin SBP and DBP show significant correlation with PiCCO but the criteria for interchangeability were not met. Finally, polar plot analysis showed that trending capabilities were excellent when changes in MAPnex (ΔMAPnex) were compared to ΔMAPfem (96.1% of changes were within the level of 10% limits of agreement). CONCLUSION: In this sample of critically ill patients we found a good correlation between MAPnex and invasive blood pressures obtained by PiCCO.

A comparison of continuous non-invasive arterial pressure with invasive radial and femoral pressure in patients undergoing cardiac surgery.

BACKGROUND: Non-invasive continous monitoring of finger arterial pressure has gained increasing interest. The aim of the present study was to compare the accuracy of non-invasive reconstructed brachial artery pressure by the Nexfin™ device (NFAP) with invasive femoral (IFAP) and radial (IRAP) artery pressure before and after cardiopulmonary bypass (CPB). METHODS: Fifty patients scheduled for elective coronary surgery were studied before and after CPB, respectively. Each patient was monitored with the non-invasive system, and both an indwelling femoral and radial arterial catheter. A passive leg raising maneuver was also performed before and after CPB. Measurements included mean (MAP), systolic (SAP) and diastolic (DAP) arterial pressure by NFAP (MAP,SAP,DAP(NFAP)), IFAP (MAP,SAP,DAP(IFAP)) and IRAP (MAP,SAP,DAP(IRAP)). Percentage changes of MAP for all measurement sites were also calculated. RESULTS: There was a moderate correlation between MAP(NFAP) and MAP(IFAP) both before (r=0.64, P<0.0001) and after (r=0.57, P<0.0001) CPB, with a percentage error (PE) of 29% and 27%, respectively. Correlation coefficients between MAP(NFAP) and MAP(IRAP) were r=0.53, P<0.0001 (PE 34%) before and r=0.54, P<0.0001 (PE 29%) after CPB. There was a significant correlation in percentage changes between ∆MAP(NFAP) and ∆MAP(IFAP) before (r=0.70, P<0.0001) and after (r=0.71, P<0.0001) CPB and for ∆MAP(NFAP) and ∆MAP(IRAP) (r=0.67, P<0.0001; r=0.74, P<0.0001), respectively. CONCLUSION: Non-invasive, reconstructed brachial artery pressure showed moderate correlation compared with both invasive femoral and radial artery pressure. Furthermore, the non-invasive monitoring system was able to reflect percentage changes in mean arterial pressure in a moderate fashion.