Respiratory variations in pulse pressure and photoplethysmographic waveform amplitude during positive expiratory pressure and continuous positive airway pressure in a model of progressive hypovolemia.

PURPOSE: Respiratory variations in pulse pressure (dPP) and photoplethysmographic waveform amplitude (dPOP) are used for evaluation of volume status in mechanically ventilated patients. Amplification of intrathoracic pressure changes may enable their use also during spontaneous breathing. We investigated the association between the degree of hypovolemia and dPP and dPOP at different levels of two commonly applied clinical interventions; positive expiratory pressure (PEP) and continuous positive airway pressure (CPAP). METHODS: 20 healthy volunteers were exposed to progressive hypovolemia by lower body negative pressure (LBNP). PEP of 0 (baseline), 5 and 10 cmH2O was applied by an expiratory resistor and CPAP of 0 (baseline), 5 and 10 cmH2O by a facemask. dPP was obtained non-invasively with the volume clamp method and dPOP from a pulse oximeter. Central venous pressure was measured in 10 subjects. Associations between changes were examined using linear mixed-effects regression models. RESULTS: dPP increased with progressive LBNP at all levels of PEP and CPAP. The LBNP-induced increase in dPP was amplified by PEP 10 cmH20. dPOP increased with progressive LBNP during PEP 5 and PEP 10, and during all levels of CPAP. There was no additional effect of the level of PEP or CPAP on dPOP. Progressive hypovolemia and increasing levels of PEP were reflected by increasing respiratory variations in CVP. CONCLUSION: dPP and dPOP reflected progressive hypovolemia in spontaneously breathing healthy volunteers during PEP and CPAP. An increase in PEP from baseline to 10 cmH2O augmented the increase in dPP, but not in dPOP.

Correction: Associations between changes in precerebral blood flow and cerebral oximetry in the lower body negative pressure model of hypovolemia in healthy volunteers.

[This corrects the article DOI: 10.1371/journal.pone.0219154.].

Volumetric and End-Tidal Capnography for the Detection of Cardiac Output Changes in Mechanically Ventilated Patients Early after Open Heart Surgery.

BACKGROUND: Exhaled carbon dioxide (CO2) reflects cardiac output (CO) provided stable ventilation and metabolism. Detecting CO changes may help distinguish hypovolemia or cardiac dysfunction from other causes of haemodynamic instability. We investigated whether CO2 measured as end-tidal concentration (EtCO2) and eliminated volume per breath (VtCO2) reflect sudden changes in cardiac output (CO). METHODS: We measured changes in CO, VtCO2, and EtCO2 during right ventricular pacing and passive leg raise in 33 ventilated patients after open heart surgery. CO was measured with oesophageal Doppler. RESULTS: During right ventricular pacing, CO was reduced by 21% (CI 18-24; p < 0.001), VtCO2 by 11% (CI 7.9-13; p < 0.001), and EtCO2 by 4.9% (CI 3.6-6.1; p < 0.001). During passive leg raise, CO increased by 21% (CI 17-24; p < 0.001), VtCO2 by 10% (CI 7.8-12; p < 0.001), and EtCO2 by 4.2% (CI 3.2-5.1; p < 0.001). Changes in VtCO2 were significantly larger than changes in EtCO2 (ventricular pacing: 11% vs. 4.9% (p < 0.001); passive leg raise: 10% vs. 4.2% (p < 0.001)). Relative changes in CO correlated with changes in VtCO2 (ρ=0.53; p=0.002) and EtCO2 (ρ=0.47; p=0.006) only during reductions in CO. When dichotomising CO changes at 15%, only EtCO2 detected a CO change as judged by area under the receiver operating characteristic curve. CONCLUSION: VtCO2 and EtCO2 reflected reductions in cardiac output, although correlations were modest. The changes in VtCO2 were larger than the changes in EtCO2, but only EtCO2 detected CO reduction as judged by receiver operating characteristic curves. The predictive ability of EtCO2 in this setting was fair. This trial is registered with NCT02070861.

Associations between changes in precerebral blood flow and cerebral oximetry in the lower body negative pressure model of hypovolemia in healthy volunteers.

Reductions in cerebral oxygen saturation (ScO2) measured by near infra-red spectroscopy have been found during compensated hypovolemia in the lower body negative pressure (LBNP)-model, which may reflect reduced cerebral blood flow. However, ScO2 may also be contaminated from extracranial (scalp) tissues, mainly supplied by the external carotid artery (ECA), and it is possible that a ScO2 reduction during hypovolemia is caused by reduced scalp, and not cerebral, blood flow. The aim of the present study was to explore the associations between blood flow in precerebral arteries and ScO2 during LBNP-induced hypovolemia. Twenty healthy volunteers were exposed to LBNP 20, 40, 60 and 80 mmHg. Blood flow in the internal carotid artery (ICA), ECA and vertebral artery (VA) was measured by Doppler ultrasound. Stroke volume for calculating cardiac output was measured by suprasternal Doppler. Associations of changes within subjects were examined using linear mixed-effects regression models. LBNP reduced cardiac output, ScO2 and ICA and ECA blood flow. Changes in flow in both ICA and ECA were associated with changes in ScO2 and cardiac output. Flow in the VA did not change during LBNP and changes in VA flow were not associated with changes in ScO2 or cardiac output. During experimental compensated hypovolemia in healthy, conscious subjects, a reduced ScO2 may thus reflect a reduction in both cerebral and extracranial blood flow.

Impact of Norepinephrine on Regional Cerebral Oxygenation During Cardiopulmonary Bypass.

OBJECTIVES: Norepinephrine is used to increase mean arterial pressure during cardiopulmonary bypass. However, it has been suggested that norepinephrine could constrict cerebral arteries, reducing cerebral blood flow. The aim of this study, therefore, was to explore whether there was an association between doses of norepinephrine to maintain mean arterial pressure at ≈80 mmHg during cardiopulmonary bypass and cerebral oxygen saturation measured using near-infrared spectroscopy. DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Patients undergoing cardiac surgery (n = 45) using cardiopulmonary bypass. INTERVENTIONS: Norepinephrine was administered to maintain mean arterial pressure ≈80 mmHg during cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: From initiation of cardiopulmonary bypass to removal of the aortic cross-clamp, norepinephrine dose, mean arterial pressure, partial pressure of arterial carbon dioxide, partial pressure of arterial oxygen, hemoglobin, and pump flow values were averaged over 1 minute, giving a total of 3,460 data points entered as covariates in a linear mixed model for repeated measurements, with cerebral oxygen saturation measured using near-infrared spectroscopy as outcome. There was no statistically significant association between norepinephrine dose to maintain mean arterial pressure and cerebral oxygen saturation (p = 0.46) in this model. CONCLUSIONS: Administration of norepinephrine to maintain mean arterial pressure ≈80 mmHg during cardiopulmonary bypass was not associated with statistically significant changes in cerebral oxygen saturation. These results indicated that norepinephrine could be used to increase mean arterial pressure during cardiopulmonary bypass without reducing cerebral oxygen saturation.

Respiratory variations in the photoplethysmographic waveform amplitude depend on type of pulse oximetry device.

Respiratory variations in the photoplethysmographic waveform amplitude predict fluid responsiveness under certain conditions. Processing of the photoplethysmographic signal may vary between different devices, and may affect respiratory amplitude variations calculated by the standard formula. The aim of the present analysis was to explore agreement between respiratory amplitude variations calculated using photoplethysmographic waveforms available from two different pulse oximeters. Analysis of registrations before and after fluid loads performed before and after open-heart surgery (aortic valve replacement and/or coronary artery bypass grafting) with patients on controlled mechanical ventilation. Photoplethysmographic (Nellcor and Masimo pulse oximeters) and arterial pressure waveforms were recorded. Amplitude variations induced by ventilation were calculated and averaged over ten respiratory cycles. Agreements for absolute values are presented in scatterplots (with least median square regression through the origin, LMSO) and Bland-Altman plots. Agreement for trending presented in a four-quadrant plot. Agreement between respiratory photoplethysmographic amplitude variations from the two pulse oximeters was poor with LMSO ΔPOPNellc = 1.5 × ΔPOPMas and bias ± limits of agreement 7.4 ± 23 %. Concordance rate with a fluid load was 91 %. Agreement between respiratory variations in the photoplethysmographic waveform amplitude calculated from the available signals output by two different pulse oximeters was poor, both evaluated by LMSO and Bland-Altman plot. Respiratory amplitude variations from the available signals output by these two pulse oximeters are not interchangeable.

Agreement between stroke volume measured by oesophageal Doppler and uncalibrated pulse contour analysis during fluid loads in severe aortic stenosis.

The purpose of this analysis was to study agreement and trending of stroke volume measured by oesophageal Doppler and 3rd generation Vigileo during fluid loads in patients with severe aortic stenosis. Observational study in 32 patients (30 analyzed) scheduled for aortic valve replacement due to severe aortic stenosis. After induction of anesthesia and before start of surgery, hemodynamic registrations for 1 min were obtained before and after a fluid load. Agreement between stroke volume measured by oesophageal Doppler (SVOD) and Vigileo (SVVig) was evaluated in Bland-Altman plot and trending in four-quadrant and polar plots. Bias ± limits of agreement (LOA) between SVOD and SVVig was 24 ± 37 ml (percentage error 45%). Concordance of the two methods from before to after a fluid load was 100%. Angular bias ± LOA was 12° ± 28°. Absolute values of SVOD and SVVig agreed poorly, but changes were highly concordant during fluid loads in aortic stenosis patients. The angular agreement indicated acceptable trending. The two measurement methods are not interchangeable in patients with aortic stenosis.

Respiratory Variations in Pulse Pressure Reflect Central Hypovolemia during Noninvasive Positive Pressure Ventilation.

Background. Correct volume management is essential in patients with respiratory failure. We investigated the ability of respiratory variations in noninvasive pulse pressure (ΔPP), photoplethysmographic waveform amplitude (ΔPOP), and pleth variability index (PVI) to reflect hypovolemia during noninvasive positive pressure ventilation by inducing hypovolemia with progressive lower body negative pressure (LBNP). Methods. Fourteen volunteers underwent LBNP of 0, -20, -40, -60, and -80 mmHg for 4.5 min at each level or until presyncope. The procedure was repeated with noninvasive positive pressure ventilation. We measured stroke volume (suprasternal Doppler), ΔPP (Finapres), ΔPOP, and PVI and assessed their association with LBNP-level using linear mixed model regression analyses. Results. Stroke volume decreased with each pressure level (-11.2 mL, 95% CI -11.8, -9.6, P < 0.001), with an additional effect of noninvasive positive pressure ventilation (-3.0 mL, 95% CI -8.5, -1.3, P = 0.009). ΔPP increased for each LBNP-level (1.2%, 95% CI 0.5, 1.8, P < 0.001) and almost doubled during noninvasive positive pressure ventilation (additional increase 1.0%, 95% CI 0.1, 1.9, P = 0.003). Neither ΔPOP nor PVI was significantly associated with LBNP-level. Conclusions. During noninvasive positive pressure ventilation, preload changes were reflected by ΔPP but not by ΔPOP or PVI. This implies that ΔPP may be used to assess volume status during noninvasive positive pressure ventilation.

Evaluation of fluid responsiveness: is photoplethysmography a noninvasive alternative?

Background. Goal-directed fluid therapy reduces morbidity and mortality in various clinical settings. Respiratory variations in photoplethysmography are proposed as a noninvasive alternative to predict fluid responsiveness during mechanical ventilation. This paper aims to critically evaluate current data on the ability of photoplethysmography to predict fluid responsiveness. Method. Primary searches were performed in PubMed, Medline, and Embase on November 10, 2011. Results. 14 papers evaluating photoplethysmography and fluid responsiveness were found. Nine studies calculated areas under the receiver operating characteristic curves for ΔPOP (>0.85 in four, 0.75-0.85 in one, and <0.75 in four studies) and seven for PVI (values ranging from 0.54 to 0.98). Correlations between ΔPOP/PVI and ΔPP/other dynamic variables vary substantially. Conclusion. Although photoplethysmography is a promising technique, predictive values and correlations with other hemodynamic variables indicating fluid responsiveness vary substantially. Presently, it is not documented that photoplethysmography is adequately valid and reliable to be included in clinical practice for evaluation of fluid responsiveness.

Proinflammatory cytokines and complement activation in salvaged blood from abdominal aortic aneurism surgery and total hip replacement surgery.

BACKGROUND: Levels of proinflammatory mediators in unwashed salvaged blood from abdominal aortic aneurism (AAA) surgery are unknown. We hypothesized that there are higher levels of these mediators in unwashed blood salvaged in AAA surgery compared to hip replacement surgery. STUDY DESIGN AND METHODS: Ten patients scheduled for AAA surgery (Group A) and 10 patients for total hip replacement surgery (Group H) were included. Blood samples from the autotransfusion set were obtained during surgery and arterial samples before, during, and 6 hours after surgery. Determination of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, activated complement 3 (C3a), and high-sensitivity C-reactive protein (CRP) were performed. Salvaged blood was not retransfused. RESULTS: Levels (median [range]) of IL-8 in blood in the salvage system were higher in Group A versus Group H (215.3 [22.5-697.2] vs. 35.3 [16.7-66.6] pg/mL; p = 0.002). Higher levels of IL-6 were also seen in Group A versus Group H (60.0 [52.6-62.2] vs. 42.34 [19.4-62.2] pg/mL; p = 0.049). Levels of IL-6 in blood sampled during surgery were approximately fivefold higher in Group A versus Group H (p = 0.023), whereas approximately 70% higher levels of C3a were observed in Group H versus Group A (p = 0.021). Postoperative concentrations of IL-1ß (p = 0.002), IL-6 (p = 0.001), and IL-8 (0.005) were higher in Group A versus Group H. CONCLUSION: Salvaged blood in AAA surgery contains substantially higher levels of proinflammatory mediators compared to blood in total hip replacement surgery.

[Anaesthesia for open-heart surgery in adults]. / Anestesi ved åpen hjertekirurgi hos voksne.

BACKGROUND: Each year, about 5 000 adults undergo heart surgery (most of them open-heart surgery) in Norway. The purpose of this overview is to address specific problems associated with anaesthesia in these patients. MATERIAL AND METHODS: The paper is based on literature identified through a non-systematic search in PubMed and own experience with clinical work and research. RESULTS: In Norway, general anaesthesia is always used in open-heart surgery. Some patients have such severely impaired heart function that it needs to be supported by inotropic drugs or mechanical devices. The patients are given heparin during surgery, and many also receive preoperative treatment with drugs that affect haemostasis. Profuse bleeding, during or after surgery, is sometimes challenging. The brain is at risk because the blood flow generated by the heart-lung machine is unphysiological, and because air or solid particles may embolize from the heart or aorta during the intervention. Renal failure after heart surgery is a serous complication with high mortality. Some anaesthetics probably have direct cardioprotective effects. Tight control of blood glucose seems to be justified, even if the level of optimal serum blood glucose is still debated. INTERPRETATION: Several organ systems are at risk during heart surgery. In addition to providing pleasant and painless sleep for the patient and good working conditions for the surgeon, the anaesthetist cooperates with the team about securing optimal organ protection.

[Choice of anaesthetic approach and anaesthetic drugs]. / Valg av anestesimetode og anestesimidler.

BACKGROUND: All types of anaesthesia should ensure absence of pain, inhibit autonomic responses and provide optimal conditions for surgery. Choice of anaesthetic approach (local, regional or general anaesthesia or a combination of methods) depends on type of surgery and the patients' health and preferences. MATERIAL AND METHODS: The review is based on literature identified through non-systematic searches in PubMed and own research and experience. RESULTS: When selecting anaesthetic approach and anaesthetic drugs one has to consider not only the perioperative period, but also postoperative aspects such as pain relief, awakeness, functional ability and absence of nausea. After major surgery, regional anaesthesia (especially epidural anaesthesia) and postoperative analgesia have been shown to reduce pulmonary complications and chronic pain. General anaesthesia can be administered either by volatile agents for inhalation, intravenous hypnotics, potent opioids or a combination (often used). Volatile agents, shown to be cardioprotective during cardiac surgery, are recommended for major non-cardiac surgery in patients with heart disease (even though clinical documentation is limited). INTERPRETATION: An appropriate anaesthetic approach, taking into account patient characteristics and type of surgery, is important for safety and potential complications. In some situations, the anaesthetic approach and anaesthetic drugs may have an impact on outcome.

Low-frequency oscillations of the laser Doppler perfusion signal in human skin.

Spectral analysis of the laser Doppler flow (LDF) signal in the frequency interval from 0.0095-2.0 Hz reveals blood flow oscillations with frequencies around 1.0, 0.3, 0.1, 0.04 and 0.01 Hz. The heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, the neurogenic activity of the vessel wall and the vascular endothelium influence these oscillations, respectively. The first aim of this study was to investigate if a slow oscillatory component could be detected in the frequency area below 0.0095 Hz of the human cutaneous blood perfusion signal. Unstimulated basal blood skin perfusion and enhanced perfusion during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were measured in healthy male volunteers and the wavelet transform was computed. A low-frequency oscillation between 0.005 and 0.0095 Hz was found both during basal conditions and during iontophoresis with ACh and SNP. Iontophoresis with ACh increased the normalized amplitude to a greater extent than SNP (P = 0.001) indicating modulation by the vascular endothelium. To gain further insight into the mechanisms for this endothelium dependency, we inhibited nitric oxide (NO) synthesis with N(G)-monomethyl-L-arginine (L-NMMA) and prostaglandin (PG) synthesis by aspirin. L-NMMA did not affect the increased response to ACh vs. SNP iontophoresis in the 0.005-0.0095-Hz interval (P = 0.006) but abolished the difference in the 0.0095-0.021-Hz interval (P = 0.97). Aspirin did not affect the difference in response to ACh and SNP in either of the two frequency intervals. Thus, other endothelial mechanisms, such as endothelium-derived hyperpolarizing factor (EDHF), might be involved in the regulation of this sixth frequency interval (0.005-0.0095 Hz).

[Heroin-induced pulmonary oedema]. / Heroinindusert lungeødem.

BACKGROUND: Heroin-induced pulmonary oedema is an infrequent complication to a heroin overdose; the incidence in Norway is unknown. MATERIAL AND METHODS: One case is presented and pathophysiology, diagnosis and treatment are discussed. RESULTS: Pulmonary oedema caused by the use of heroin may develop immediately or usually up to 1-2 hours after exposure. The symptoms usually resolve with supportive treatment within 1 or 2 days. Some patients require mechanical ventilation. The pathophysiology includes a rapid capillary leakage of unknown aetiology. INTERPRETATION: Heroin use is widespread in Norway, and users are found all over the country. There are important differences between cardiogenic and heroin-induced pulmonary oedema regarding pathophysiology and treatment.

Enhanced endothelial activity reflected in cutaneous blood flow oscillations of athletes.

Functional alterations of vascular endothelial cells may be evaluated by analysing differences in effects of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilators. We evaluated whether a dynamic approach using spectral analysis of the blood flow signal, resulting from the cutaneous red cell flux and recorded by the technique of laser Doppler flowmetry (LDF), can detect higher endothelial responsiveness in trained versus less trained individuals. There was a 1.6 times higher ACh-induced cutaneous perfusion in athletes than in controls ( P<0.05), both when evaluated as a mean value of the LDF signal or as the amplitudes of its spectral components. In the frequency interval from 0.009 to 1.6 Hz, ACh induced a 1.6 times higher average spectral amplitude ( P<0.01) in athletes compared with controls. ACh also induced a 1.6 times higher absolute spectral amplitude of the oscillator at around 0.01 Hz ( P<0.05) in the athletes compared with the controls, whereas the endothelial oscillation at around 0.01 Hz during basal unstimulated perfusion was 1.5 times higher ( P<0.01). There were no significant differences in absolute or relative amplitude during iontophoresis with SNP. These results indicate that athletes have higher endothelial activity than less trained individuals.

Regulation of human cutaneous circulation evaluated by laser Doppler flowmetry, iontophoresis, and spectral analysis: importance of nitric oxide and prostaglandines.

Nitric oxide (NO) and prostaglandines (PGs) are important in regulation of vascular tone and blood flow. Their contribution in human cutaneous circulation is still uncertain. We inhibited NO synthesis by infusing N(G)-monomethyl-L-arginine (L-NMMA) in the brachial artery (16 micromol/min for 5 min) and reversed it by intraarterial infusion of L-arginine (40 micromol/min for 7.5 min). PG synthesis was inhibited by the cyclooxygenase inhibitor aspirin (600 mg over 5 min intravenously). Basal cutaneous perfusion and perfusion responses during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were recorded by laser Doppler flowmetry (LDF). We performed wavelet transforms of the measured signals. Mean spectral amplitude within the frequency interval from 0.0095 to 1.6 Hz and mean and normalized amplitudes of five intervals around 1, 0.3, 0.1, 0.04, and 0.01 Hz were analysed. The oscillations with frequencies around 1, 0.3, 0.1, and 0.04 Hz are influenced by the heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, and the neurogenic activity of the vessel wall, respectively. We have previously shown that the oscillation with a frequency around 0.01 Hz is modulated by the vascular endothelium. L-NMMA reduced mean value of the LDF signal by approximately 20% (P = 0.0067). This reduction was reversed by L-arginine. Mean value of the LDF signals during ACh and SNP iontophoresis did not change after infusion of L-NMMA. Aspirin did not affect mean value of the LDF signal or the LDF signal during ACh or SNP iontophoresis. Before interventions the only significant difference between the effects of ACh and SNP was observed in the frequency around 0.01 Hz, where ACh increased normalized amplitude to a greater extent than SNP. L-NMMA abolished this difference, whereas it reappeared after infusion of L-arginine (P = 0.0084). Aspirin did not affect this difference (P = 0.006). We conclude that basal cutaneous blood flow and the endothelial dependency of the oscillation around 0.01 Hz are partly mediated by NO, but not by endogenous PGs. Other aspects of human cutaneous circulation studied are not regulated by NO or PGs.

Preconditioning - endogenous defence mechanisms of the heart.

The term 'preconditioning' refers to the paradoxical phenomenon that pretreatment with a potential noxious stress-stimulus can increase cellular tolerance to subsequent noxious stress-stimuli. This was first described in an experimental model in dogs in which short-lasting periods of myocardial ischemia resulted in reduced infarction during a subsequent long-lasting coronary artery occlusion. Similar observations have also been made in other species and in other organs. During the last few years, the term preconditioning has been expanded to include pretreatment with other physical stress-stimuli or pharmacological agents that can increase cellular resistance to injury. The phenomenon probably represents a general adaptive response to cellular stress, but mechanisms involved are not fully clarified. This review focuses on preconditioning in the heart. Firstly, we want to address the observation that activation of endogenous defence mechanisms can increase cellular tolerance to several potentially noxious stimuli. Based on results from experimental research, we will give an overview of intracellular mechanisms that is currently in focus. Secondly, we want to address the potential role of preconditioning in clinical practice. We will present results from studies in patients with coronary artery disease and discuss possible clinical implications. Results show that the phenomenon probably exists in the human myocardium. In the future, this might be exploited in patients with acute coronary syndromes, especially since advanced techniques are now available for acute revascularization. Additionally, identification of possible mechanisms involved may influence the choice of medical treatment in high-risk patients with stable coronary artery disease. Preconditioning can also be exploited during elective surgical procedures. This should be of great interest, as the extent of elective surgery in patients at high-risk for coronary events is increasing. In this respect it is important to note that opioid-receptors are probably involved in preconditioning in humans. The last part of this review will address the possible relation between preconditioning and different anesthetic agents and sedatives.