Vincent Castelain

Haemodynamic evaluation of pulmonary hypertension

Pulmonary hypertension is characterised by the chronic elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) leading to right ventricular enlargement and hypertrophy. Pulmonary hypertension may result from respiratory and cardiac diseases, the most severe forms occurring in thromboembolic and primary pulmonary hypertension. Pulmonary hypertension is most often defined as a mean PAP >25 mmHg at rest or >30 mmHg during exercise, the pressure being measured invasively with a pulmonary artery catheter. Doppler echocardiography allows serial, noninvasive follow-up of PAPs and right heart function. When the adaptive mechanisms of right ventricular dilatation and hypertrophy cannot compensate for the haemodynamic burden, right heart failure occurs and is associated with poor prognosis. The haemodynamic profile is the major determinant of prognosis. In both primary and secondary pulmonary hypertension, special attention must be paid to the assessment of pulmonary vascular resistance index (PVRI), right heart function and pulmonary vasodilatory reserve. Recent studies have stressed the prognostic values of exercise capacity (6-min walk test), right atrial pressure, stroke index and vasodilator challenge responses, as well as an interest in new imaging techniques and natriuretic peptide determinations. Overall, careful haemodynamic evaluation may optimise new diagnostic and therapeutic strategies in pulmonary hypertension.

Evaluation of Various Empirical Formulas for Estimating Mean Pulmonary Artery Pressure by Using Systolic Pulmonary Artery Pressure in Adults

BACKGROUND Mean pulmonary artery pressure (mPAP) may be estimated by using the classic rule of thumb, namely 2/3 x dPAP + 1/3 x sPAP, where dPAP = diastolic PAP and sPAP = systolic PAP. Studies have suggested that mPAP may be also estimated from sPAP alone. Pulmonary hypertension (PH) is usually defined by an invasive mPAP > 25 mm Hg, but the corresponding sPAP threshold remains to be established. Our study evaluated the accuracy and precision of various empirical formulas relating mPAP and sPAP in resting adults. METHODS Five previously published studies with individual high-fidelity PAPs were analyzed (n = 166 individuals, 57% of whom had PH). The time-averaged mPAP was compared with formula one (F1), the classic rule of thumb; formula two (F2) = dPAP + 0.41 x pulse PAP; formula three (F3) = square root of (sPAP x dPAP); formula four (F4) = 0.61 x sPAP + 2 mm Hg; and formula five (F5) = 2/3 x sPAP (parabolic shape). RESULTS The mPAP ranged from 9 to 82 mm Hg and was related to sPAP (r(2) = 0.98). The most accurate formula was F4 (mean bias, 0.0 mm Hg). The most precise formula was F1 (SD of the bias, 1.6 mm Hg). Other formulas gave estimates of essentially similar accuracy, while F2 and F3 were more precise than F4 and F5. sPAP > 36 mm Hg could be used to diagnose PH (mPAP > 25 mm Hg) with a 97.9% sensitivity and 98.6% specificity. CONCLUSION In resting adults, the most accurate estimate of mPAP was obtained by using sPAP only, while the combination of sPAP and dPAP gave the most precise mPAP estimate. The sPAP threshold of 36 mm Hg could be used to diagnose PH with high sensitivity and high specificity.

Serum concentration of chromogranin A at admission : An early biomarker of severity in critically ill patients

Background. Chromogranin A (CGA), a stress marker released with catecholamines by the adrenal medulla, has never been associated with acute inflammation in critically ill patients. Aim. To determine evidence for a link between serum concentration of CGA, biomarkers of inflammation, and outcome in patients admitted with or without the systemic inflammatory response syndrome (SIRS). Methods. At admission, we measured in 53 patients and 14 healthy controls the serum concentrations of CGA, procalcitonin, and C-reactive protein. We also assessed the Simplified Acute Physiological Score (SAPS) in the patients. Results. Serum CGA concentrations were significantly increased in SIRS patients with a median value of 115 µg/L (68.0–202.8), when compared to healthy controls (P<0.001). In cases where infection was associated with SIRS, patients had the highest increase in CGA with a median value of 138.5 µg/L (65–222.3) (P<0.001). CGA concentrations positively correlated with inflammation markers (procalcitonin, C-reactive protein), but also with SAPS. Receiver operating characteristic (ROC) analysis showed that CGA is equivalent to SAPS as an indicator for 28-day mortality (area under curve (AUC) for both: 0.810). Conclusions. Patients with CGA concentration superior to 71 µg/L have a significantly shorter survival. A Cox model confirmed that CGA and SAPS were independent predictors of outcome.

Prognostic Value of Chromogranin A at Admission in Critically Ill Patients: A Cohort Study in a Medical Intensive Care Unit

BACKGROUND Risk assessments of patients should be based on objective variables, such as biological markers that can be measured routinely. The acute response to stress causes the release of catecholamines from the adrenal medulla accompanied by chromogranin A (CGA). To date, no study has evaluated the prognostic value of CGA in critically ill intensive care unit patients. METHODS We conducted a prospective study of intensive care unit patients by measuring serum procalcitonin (PCT), C-reactive protein (CRP), and CGA at the time of admission. Univariate and multivariate analyses were performed to evaluate the ability of these biomarkers to predict mortality. RESULTS In 120 consecutive patients, we found positive correlations between CGA and the following: CRP (r(2) = 0.216; P = 0.02), PCT (r(2) = 0.396; P < 0.001), Simplified Acute Physiologic Score II (SAPS II) (r(2) = 0.438; P < 0.001), and the Logistic Organ Dysfunction System (LODS) score (r(2) = 0.374; P < 0.001). Nonsurvivors had significantly higher CGA and PCT concentrations than survivors [median (interquartile range): 293.0 microg/L (163.5-699.5 microg/L) vs 86.0 microg/L (53.8-175.3 microg/L) for CGA, and 6.78 microg/L (2.39-22.92 microg/L) vs 0.54 microg/L (0.16-6.28 microg/L) for PCT; P < 0.001 for both comparisons]. In a multivariable linear regression analysis, creatinine (P < 0.001), age (P < 0.001), and SAPS II (P = 0.002) were the only significant independent variables predicting CGA concentration (r(2) = 0.352). A multivariate Cox regression analysis identified 3 independent factors predicting death: log-normalized CGA concentration [hazard ratio (HR), 7.248; 95% confidence interval (CI), 3.004-17.487], SAPS II (HR, 1.046; 95% CI, 1.026-1.067), and cardiogenic shock (HR, 3.920; 95% CI, 1.731-8.880). CONCLUSIONS CGA is a strong and independent indicator of prognosis in critically ill nonsurgical patients.

Estimating Right Ventricular Stroke Work and the Pulsatile Work Fraction in Pulmonary Hypertension

BACKGROUND The mean pulmonary artery pressure (mPAP) replaces mean systolic ejection pressure (msePAP) in the classic formula of right ventricular stroke work (RVSW) = (mPAP - RAP) × stroke volume, where RAP is mean right atrial pressure. Only the steady work is thus taken into account, not the pulsatile work, whereas pulmonary circulation is highly pulsatile. Our retrospective, high-fidelity pressure study tested the hypothesis that msePAP was proportional to mPAP, and looked at the implications for RVSW. METHODS Eleven patients with severe, precapillary pulmonary hypertension (PH) (six patients with idiopathic pulmonary arterial hypertension and five with chronic thromboembolic PH; mPAP = 57 ± 10 mm Hg) were studied at rest and during mild to moderate exercise. Eight non-PH control subjects were also studied at rest (mPAP = 16 ± 2 mm Hg). The msePAP was averaged from end diastole to dicrotic notch. RESULTS In the full data set (53 pressure-flow points), mPAP ranged from 14 to 99.5 mm Hg, cardiac output from 2.38 to 11.1 L/min, and heart rate from 53 to 163 beats/min. There was a linear relationship between msePAP and mPAP (r² = 0.99). The msePAP matched 1.25 mPAP (bias, -0.5 ± 2.6 mm Hg). Results were similar in the resting non-PH group and in resting and the exercising PH group. This implies that the classic formula markedly underestimates RVSW and that the pulsatile work may be a variable 20% to 55% fraction of RVSW, depending on RAP and mPAP. At rest, RVSW in patients with PH was twice as high as that of the non-PH group (P < .05), but pulsatile work fraction was similar between the two groups (26 ± 4% vs 24 ± 1%) because of the counterbalancing effects of high RAP (11 ± 5 mm Hg vs 4 ± 2 mm Hg), which increases the fraction, and high mPAP, which decreases the fraction. CONCLUSIONS Our study favored the use of an improved formula that takes into account the variable pulsatile work fraction: RVSW = (1.25 mPAP - RAP) × stroke volume. Increased RAP and increased mPAP have opposite effects on the pulsatile work fraction.

Strong linear relationship between heart rate and mean pulmonary artery pressure in exercising patients with severe precapillary pulmonary hypertension

The contribution of heart rate (HR) to pulmonary artery hemodynamics has been suggested in pulmonary hypertension (PH). Our high-fidelity pressure, retrospective study tested the hypothesis that HR explained the majority of mean pulmonary artery pressure (mPAP) and pulse pressure (PApp) variation in 12 severe precapillary PH patients who performed incremental-load cycling while in the supine position. Seven idiopathic pulmonary arterial hypertension patients and five chronic thromboembolic PH patients were studied. Four to five PAP-thermodilution cardiac output (CO) points (mean: 4.4) were obtained. At rest, mPAP was 57 ± 9 mmHg, PApp was 51 ± 11 mmHg, HR was 90 ± 12 beats/min, and stroke volume (SV) was 50 ± 22 ml. At peak exercise, mPAP was 76 ± 10 mmHg, PApp was 67 ± 11 mmHg, and HR was 123 ± 18 beats/min (i.e., 71 ± 10% of maximum HR, each P < 0.05), whereas SV was 51 ± 20 ml (P = not significant). The input resistance did not change (mPAP/CO = 14.1 ± 4.1 vs. 13.5 ± 4.4 mmHg·min·l(-1)). The relative increase in mPAP was related to the relative increase in HR (n = 12, r(2) = 0.74) but not in CO. mPAP was linearly related to CO in 8 of 12 patients (median r(2) = 0.83) and to HR in 12 of 12 patients (median r(2) = 0.985). The parsimony principle favored the latter fit. PApp was linearly related to mPAP in 12 of 12 patients (median r(2) = 0.985), HR in 10 of 12 patients (median r(2) = 0.97), CO in 7 of 12 patients (median r(2) = 0.87), and SV in 1 of 12 patients. A strong linear relationship between HR and mPAP was consistently documented in severe precapillary PH patients who performed supine exercise. The limited value of thermodilution CO to predict mPAP could be explained by unavoidable precision errors in CO measurements, unchanged/decreased SV on exercise, curvilinearity of the mPAP-CO relationship at high flow, or flow-independent additional mechanisms increasing mPAP on exercise.

Pulse wave reflection in pulmonary hypertension

In a recent Journal study, Nakayama et al. [(1)][1]showed that patients with chronic pulmonary thromboembolism (CPTE) had a higher pulmonary artery augmentation index and shorter inflection time than patients with primary pulmonary hypertension (PPH). Data were obtained on a large study population

Life-threatening cervical necrotizing fasciitis after a common dental extraction.

We report a case of cervical necrotizing fasciitis (NF) with severe sepsis occurring 8 hours after a banal dental extraction in a healthy adult. A 44-year-old man was admitted for cervical NF and severe sepsis in the emergency department. An early diagnosis was based on clinical examination (violent pain, swelling of face, and crepitation), confirmed by computed tomography scan, which showed subcutaneous gas and a fracture of the maxillary sinus in regard of the extracted tooth. Broad spectrum antibiotherapy was started quickly followed by surgical debridement. Operative and sinus pus cultures were positive for polymicrobial strains (aerobes and anaerobe). Ventilatory and hemodynamic supports (large fluid infusion and catecholamine) were mandatory during a week. Successful outcome occurred within 2 weeks. Cervical NF is a rare but life-threatening disease with fulminant course. The mortality rate is high if the diagnosis and treatment are not begun promptly and vigorously. Therefore, the emergency medicine community must be aware of its initial symptoms.

Emergency step-by-step specific immunotherapy in severe digoxin poisoning: an observational cohort study.

Objective To evaluate the efficacy and safety of a step-by-step fixed dose of specific immunotherapy protocol in case of severe digoxin poisoning in an open uncontrolled prospective study. Methods Twenty consecutive patients were admitted because of severe digoxin poisoning. The inclusion criteria were: digoxin overdose and either life-threatening arrhythmia; high-degree atrioventricular block, ventricular arrhythmia, or bradycardia less than 50 bpm and hyperkalaemia (>5.5 mmol/l). A two-step protocol of antidigoxin antibodies treatment was carried out. At admission, every patient received two vials of specific Fab-fragments. If after 1 h following infusion ECG signs regressed, no more treatment was given. If ECG signs did not regress, patients were given two more vials. At inclusion and 6 h after immunotherapy, clinical (cardiac rhythm, ECG records) and biological (serum digoxin concentration, potassium) findings were recorded. Results Patients had a median (interquartile range) age of 83 (75–90) years. Four patients had acute poisoning and 16 chronic overdoses. Eleven patients showed ventricular arrhythmia, and five had high-degree atrioventricular block. Seventy percent of the patients needed only the first step. Significant decreases were observed in the number of cardiac dysrhythmia (16 vs. three patients), in the median (interquartile range) of serum digoxin concentration [5 μg/l (3.8–6.2) vs. 0.4 μg/l (0.3–2.2)] and in serum potassium [4.6 mmol/l (4.1–5.5) vs. 3.85 mmol/l (3.7–4.55)] before and after immunotherapy. The digoxin-related mortality was 5%. Conclusion This protocol of step-by-step digoxin-specific immunotherapy seems to be as effective as the equimolar treatment, and there was significant cost reduction in case of acute poisoning.

Letter to the editor: “Pulsatile pulmonary artery pressure: are fluid-filled catheters accurate in pulmonary hypertension?”

to the editor: We have read with interest the article “Decreased time constant of the pulmonary circulation in chronic thromboembolic pulmonary hypertension,” by MacKenzie Ross et al. ([6][1]). Using fluid-filled catheters, the authors have documented that the pulmonary arterial time constant is