Persistent Fever and Positive PCR 90 Days Post-SARS-CoV-2 Infection in a Rituximab-Treated Patient: A Case of Late Antiviral Treatment.

Background: Persistent fever after SARS-CoV-2 infection in rituximab-treated patients has been reported. Due to reduced sensitivity in conventional sampling methods and unspecific symptoms in these patients, distinguishing between low-grade viral replication or hyperinflammation is challenging. Antiviral treatment is recommended as prophylactic or early treatment in the at-risk population; however, no defined treatment approaches for protracted SARS-CoV-2 infection exist. Results: We present a case of 96 days of persistent fever and SARS-CoV-2 infection in a patient receiving B cell depletion therapy for multiple sclerosis. Migratory lung infiltrates and positive PCR tests from serum (day-58 post infection) and lower airways (day-90 post infection) confirmed continuous viral replication. The dominant symptoms were continuous high fever, dyspnea and mild to moderate hypoxemia, which never developed into severe respiratory failure. The patient was hospitalized three times, with transient improvement after late antiviral treatment and full recovery 6 months post-rituximab infusion. Conclusions: A strategy for securing samples from lower airways and serum should be a prioritization to strengthen diagnostic certainty in immunocompromised patients. B-cell-deprived patients could benefit from late treatment with SARS-CoV-2-specific monoclonal antibodies and antivirals. Importantly, increased intervals between immunosuppressive therapy should be considered where feasible.

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.

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.

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.].

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.

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.

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.

Tissue oxygen saturation and finger perfusion index in central hypovolemia: influence of pain.

OBJECTIVES: Tissue oxygen saturation and peripheral perfusion index are proposed as early indirect markers of hypovolemia in trauma patients. Hypovolemia is associated with increased sympathetic nervous activity. However, many other stimuli, such as pain, also increase sympathetic activity. Since pain is often present in trauma patients, its effect on the indirect measures of hypovolemia needs to be clarified. The aim of this study was, therefore, to explore the effects of hypovolemia and pain on tissue oxygen saturation (measurement sites: cerebral, deltoid, forearm, and thenar) and finger photoplethysmographic perfusion index. DESIGN: Experimental study. SETTING: University hospital clinical circulation and research laboratory. SUBJECTS: Twenty healthy volunteers. INTERVENTIONS: Central hypovolemia was induced with lower body negative pressure (-60 mm Hg) and pain by the cold pressor test (ice water exposure). Interventions were performed in a 2×2 fashion with the combination of lower body negative pressure or not (normovolemia), and ice water or not (sham). Each subject was thus exposed to four experimental sequences, each lasting for 8 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements were averaged over 30 seconds. For each person and sequence, the minimal value was analyzed. Tissue oxygenation in all measurement sites and finger perfusion index were reduced during hypovolemia/sham compared with normovolemia/sham. Tissue oxygen saturation (except cerebral) and perfusion index were reduced by pain during normovolemia. There was a larger reduction in tissue oxygenation (all measurement sites) and perfusion index during hypovolemia and pain than during normovolemia and pain. CONCLUSIONS: Pain (cold pressor test) reduces tissue oxygen saturation in all measurement sites (except cerebral) and perfusion index. In the presence of pain, tissue oxygen saturation and perfusion index are further reduced by hypovolemia (lower body negative pressure, -60 mm Hg). Thus, pain must be considered when evaluating tissue oxygen saturation and perfusion index as markers of hypovolemia in trauma patients.

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.

Nitrous oxide for analgesia in colonoscopy without sedation.

BACKGROUND: Colonoscopy is associated with pain and discomfort, and intravenous analgesics and sedatives are widely used. There are several disadvantages regarding this practice, including risk of complications, resources demanded, and amnesia after sedation. In spite of promising results in previous studies, nitrous oxide is rarely used at endoscopy centers around the world. OBJECTIVE: To investigate the efficiency of nitrous oxide versus placebo as an analgesic during colonoscopy without sedation. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: The endoscopy unit at Oslo University Hospital Rikshospitalet, Oslo, Norway, between June 2006 and May 2008. PATIENTS: This study involved patients undergoing elective colonoscopy. INTERVENTION: Patients inhaled nitrous oxide or placebo on demand. MAIN OUTCOME MEASUREMENTS: The participants filled in a questionnaire regarding their experiences with the examination. Pain was graded from 1 (no pain) to 4 (severe pain). RESULTS: We recruited 199 patients. We randomized 97 patients to the nitrous oxide group and 102 to the control group. The groups were comparable regarding demographic factors. Median patient-reported pain was 2 in both the nitrous oxide group and the control group (interquartile range 2-3 in both groups). Additional sedatives and analgesics were given equally often and in similar doses in both groups. No side effects related to administration of nitrous oxide were reported. LIMITATIONS: The questionnaire was returned by 76% of the patients. The study gas was given on demand, not continuously. CONCLUSION: Nitrous oxide given intermittently is not an effective substitution for intravenous on-demand sedation and analgesics in the setting of colonoscopy without sedation.