Heart-lung interactions: Implications for non-invasive evaluation of changes in blood volume

Loss in blood volume due to bleeding or critical illness may be difficult to detect based on clinical signs such as blood pressure and heart rate alone. Monitoring of cardiac output is recommended for haemodynamic evaluation, but methods are often invasive and skill-dependent. However, peripheral circulatory and ventilatory changes following heart-lung interactions may reflect central hypovolemia. Heart-lung interactions may be recognizable as respiratory induced changes in pulse pressure and the photoplethysmographic waveform amplitude; referred to as “dynamic variables”. Dynamic variables have been found to reliably predict volume changes during mechanical ventilation. Mechanical ventilation induces regular cyclic changes in intrathoracic pressure, and is assumed to be a prerequisite for the use of dynamic variables. Change in exhaled carbon dioxide is another dynamic measure of heart-lung interactions which has been shown to reflect large changes in cardiac output, mostly in experimental studies. The aims of this thesis were to explore less invasive methods based on heart-lung interactions in new experimental and clinical settings. In two different experimental studies on healthy volunteers we found that dynamic variables revealed blood loss induced by lower body negative pressure also during non-invasive positive pressure ventilation and positive expiratory pressure; two frequently used clinical interventions. In a clinical study on patients after open heart surgery we found that changes in exhaled CO2 accurately reflected moderate reductions in cardiac output induced by right ventricular pacing. These findings indicate that dynamic variables may be applicable also in patients without mechanical ventilation and obtainable by less invasive monitoring than previously assumed. This may enable earlier identification of hypovolemia due to for instance bleeding also in patients without invasive monitoring

Prioritering i spesialisthelsetjenesten : målsetninger, virkemidler og effekter.

Prioriteringsarbeidet har pågått i Norge i ca 30 år. Helsegapet, diskrepansen mellom hva som er medisinsk / teknologisk mulig og hva som er økonomisk mulig tilsier at behovet for tydeligere prioriteringer øker. Lik tilgang til helsetjenesten ved like behov, utjevning av sosiale forskjeller i helse og mest mulig helse for pengene er sentrale målsetninger for helsetjenesten. Disse har delvis motstridende implikasjoner, og en avklaring av målsetninger er nødvendig. Det samme gjelder de overordnede kriteriene for rett til nødvendig helsehjelp etter Pasientrettighetslovens #2. Tidligere ble alvorlighetskriteriet tillagt mest vekt, nå synes tiltakets nytte og kostnadseffektivitet å være viktigere kriterier. Imidlertid mangler standardiserte metoder for beregning av helsegevinst, og QALY-konseptet kunne med fordel vært mer brukt. Myndighetene har styringsverktøy av politisk, juridisk og økonomisk art. Foretaksreformen, pasientrettighetsloven og innføring av ISF/DRG har vært blant de viktigste hendelsene i prioriteringssammenheng, men effektene er ikke entydige. Mange utfordringer gjenstår, bl.a. er det behov for tydeligere politisk avklaring i prioriteringsspørsmålet. Dessuten har virkemidlene delvis uønskede effekter som motvirker overordnede målsetninger. Prioriteringsarbeidet synes også å ha begrenset gjennomslag til foretaks- og behandlernivå der den praktiske prioriteringen skal skje

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 (p = 0.53; p = 0.002) and EtCO2 (p = 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

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

Cardiac power parameters during hypovolemia, induced by the lower body negative pressure technique, in healthy volunteers

Background Changes in cardiac power parameters incorporate changes in both aortic flow and blood pressure. We hypothesized that dynamic and non-dynamic cardiac power parameters would track hypovolemia better than equivalent flow- and pressure parameters, both during spontaneous breathing and non-invasive positive pressure ventilation (NPPV). Methods Fourteen healthy volunteers underwent lower body negative pressure (LBNP) of 0, −20, −40, −60 and −80 mmHg to simulate hypovolemia, both during spontaneous breathing and during NPPV. We recorded aortic flow using suprasternal ultrasound Doppler and blood pressure using Finometer, and calculated dynamic and non-dynamic parameters of cardiac power, flow and blood pressure. These were assessed on their association with LBNP-levels. Results Respiratory variation in peak aortic flow was the dynamic parameter most affected during spontaneous breathing increasing 103 % (p < 0.001) from baseline to LBNP −80 mmHg. Respiratory variation in pulse pressure was the most affected dynamic parameter during NPPV, increasing 119 % (p < 0.001) from baseline to LBNP −80 mmHg. The cardiac power integral was the most affected non-dynamic parameter falling 59 % (p < 0.001) from baseline to LBNP −80 mmHg during spontaneous breathing, and 68 % (p < 0.001) during NPPV. Conclusions Dynamic cardiac power parameters were not better than dynamic flow- and pressure parameters at tracking hypovolemia, seemingly due to previously unknown variation in peripheral vascular resistance matching respiratory changes in hemodynamics. Of non-dynamic parameters, the power parameters track hypovolemia slightly better than equivalent flow parameters, and far better than equivalent pressure parameters

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.]

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

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

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7