Lung ultrasound for early diagnosis of postoperative need for ventilatory support: a prospective observational study.

Pulmonary complications have a significant impact on morbidity and mortality in patients after major surgery. Lung ultrasound can be used at the bed-side, and has gained widespread acceptance in the intensive care unit. We conducted a prospective study to evaluate whether lung ultrasound could be used as a predictive marker for postoperative ventilatory support in high-risk surgical patients. We included 109 patients admitted to the intensive care unit while having mechanical ventilation of the lungs following major surgery. The PaO2 /FI O2 ratio was calculated on admission and an ultrasound examination performed, including: lung ('lung ultrasound score', number of consolidated lung areas); cardiac (mitral flow); and inferior vena cava imaging (diameter and respiratory variation). Respiratory outcomes included: the need for ventilation support (mechanical ventilation, non-invasive ventilation or high-flow nasal cannula oxygen therapy); acute respiratory distress syndrome; cardiogenic pulmonary oedema; and early or late pulmonary infection. Patients with a lung ultrasound score ≥ 10 had a lower PaO2 /FI O2 ratio, and needed more postoperative ventilatory support, than patients with lung ultrasound score < 10. Twenty patients had acute respiratory distress syndrome, and 14 had cardiogenic pulmonary oedema. The presence of ≥ 2 areas of consolidated lung was associated with a lower PaO2 /FI O2 ratio, postoperative ventilatory support, longer intensive care stay and episodes of ventilator-associated pneumonia requiring antibiotics. Our results suggest that at intensive care unit admission, lung ultrasound scoring and detection of atelectasis can predict postoperative pulmonary outcomes after major visceral surgery, and could enhance bed-side decision making.

Dynamic arterial elastance measured by uncalibrated pulse contour analysis predicts arterial-pressure response to a decrease in norepinephrine.

BACKGROUND: Dynamic arterial elastance (Eadyn) has been proposed as an indicator of vascular tone that predicts the decrease in arterial pressure in response to changes in norepinephrine (NE). The purpose of this study was to determine whether Eadyn measured by uncalibrated pulse contour analysis (UPCA) can predict a decrease in arterial pressure when the NE dosage is decreased. METHODS: We conducted a prospective study in a university hospital intensive care unit. Patients with vasoplegic syndrome for whom the intensive care physician planned to decrease the NE dosage were included. Haemodynamic and UPCA (VolumeView and FloTrac; Edwards Lifesciences, Irvine, CA, USA) values were obtained before and after decreasing the NE dosage. Responders were defined by a >10% decrease in mean arterial pressure (MAP). RESULTS: Of 35 patients included, 11 (31%) were pressure responders with a median decrease of 13%. Eadyn was correlated to systolic arterial pressure (SAP) (r=0.255; P=0.033), diastolic arterial pressure (r=0.271; P=0.024), MAP (r=0.310; P=0.009), heart rate (r=0.543; P=0.0001), and transthoracic echography cardiac output (r=0.264; P=0.024). Baseline Eadyn was correlated with MAP changes (r=0.394; P=0.019) and SAP changes (r=0.431; P=0.009). Eadyn predicted the decrease in arterial pressure with an area under the receiver-operating-characteristic curve of 0.84 (95% confidence interval: 0.70-0.97). The best cut-off was 0.90. CONCLUSIONS: The present study confirms the ability of Eadyn measured by UPCA to predict an arterial pressure response to a decrease in NE. Eadyn may constitute an easy-to-use functional approach to arterial tone assessment regardless of the monitor used to measure its determinant. CLINICAL TRIAL REGISTRATION: DRCIT95.

Respiratory stroke volume variation assessed by oesophageal Doppler monitoring predicts fluid responsiveness during laparoscopy.

BACKGROUND: This study was designed to assess the ability of the stroke volume respiratory variation (ΔrespSV) determined by oesophageal Doppler monitoring (ODM) to predict the response to volume expansion (VE) during pneumoperitoneum. The predictive value of ΔrespSV was evaluated according to the concept of the 'grey zone'. METHODS: Patients operated on laparoscopy and monitored by ODM were prospectively included. The exclusion criteria were frequent ectopic beats or preoperative arrhythmia, right ventricular failure, and spontaneous breathing. Haemodynamic parameters and oesophageal Doppler indices [stroke volume (SV), peak velocity (PV), cardiac output (CO), corrected flow time (FTc), respiratory variation of PV (ΔrespPV) and SV (ΔrespSV)] were collected before and after VE. Responders were defined as a ≥15% increase in SV after VE. RESULTS: Thirty-eight (64%) of the 59 patients were responders. A cut-off of >14% ΔrespSV predicted fluid responsiveness with an area under the ROC curve (AUC) of 0.92 [95% confidence interval (CI): 0.82-0.98, P<0.0001]. The grey zone of ΔrespSV ranged between 13 and 15%. With an AUC of 0.71 (95% CI: 0.56-0.83, P=0.005), ΔrespPV fairly accurately predicted fluid responsiveness. FTc was unable to accurately predict fluid responsiveness. CONCLUSIONS: ΔrespSV and ΔrespPV predicted fluid responsiveness during laparoscopy under strict physiological conditions. FTc was not predictive of fluid responsiveness during laparoscopy.

End-expiratory occlusion manoeuvre does not accurately predict fluid responsiveness in the operating theatre.

BACKGROUND: The objective of this study was to determine whether assessment of stroke volume (SV) and measurement of exhaled end-tidal carbon dioxide [Formula: see text] during an end-expiratory occlusion (EEO) test can predict fluid responsiveness in the operating theatre. METHODS: Forty-two subjects monitored by oesophageal Doppler who required i.v. fluids during surgery were studied. Haemodynamic variables [heart rate, non-invasive arterial pressure, SV, cardiac output (CO), respiratory variation of SV (ΔrespSV), variation of SV during EEO, and E'(CO2) were measured at baseline, during EEO (Δ(EEO)), and after fluid expansion. Responders were defined by an increase in SV over 15% after infusion of 500 ml of crystalloid solution. RESULTS: Of the 42 subjects, 28 (67%) responded to fluid infusion. A cut-off of >2.3% ΔSV(EEO) predicted fluid responsiveness with an area under the receiver-operating characteristic (AUC) curve of 0.78 [95% confidence interval (95% CI): 0.63-0.89, P=0.003]. The AUC of ΔrespSV was 0.89 (95% CI: 0.76-0.97, P<0.001). With an AUC of 0.68 (95% CI: 0.51-0.81, P=0.07), E'(CO2)(EEO) was poorly predictive of fluid responsiveness. CONCLUSIONS: ΔSV(EEO) and ΔE'(CO2) were unable to accurately predict fluid responsiveness during surgery.

Accuracy of impedance cardiography for evaluating trends in cardiac output: a comparison with oesophageal Doppler.

BACKGROUND: Impedance cardiography (ICG) enables continuous, beat-by-beat, non-invasive, operator-independent, and inexpensive cardiac output (CO) monitoring. We compared CO values and variations obtained by ICG (Niccomo™, Medis) and oesophageal Doppler monitoring (ODM) (CardioQ™, Deltex Medical) in surgical patients. METHODS: This prospective, observational, single-centre study included 32 subjects undergoing surgery with general anaesthesia. CO was measured simultaneously with ICG and ODM before and after events likely to modify CO (vasopressor administration and volume expansion). One hundred and twenty pairs of CO measurements and 94 pairs of CO variation measurements were recorded. RESULTS: The CO variations measured by ICG correlated with those measured by ODM [r=0.88 (0.82-0.94), P<0.001]. Trending ability was good for a four-quadrant plot analysis with exclusion of the central zone (<10%) [95% confidence interval (CI) for concordance (0.86; 1.00)]. Moderate to good trending ability was observed with a polar plot analysis (angular bias: -7.2°; 95% CI -12.3°; -2.5°; with radial limits of agreement -38°; 24°). After excluding subjects with chronic obstructive pulmonary disease, a Bland-Altman plot showed a mean bias of 0.47 litre min(-1), limits of agreements between -1.24 and 2.11 litre min(-1), and a percentage error of 35%. CONCLUSION: ICG appears to be a reliable method for the non-invasive monitoring of CO in patients undergoing general surgery.

Ability of stroke volume variation measured by oesophageal Doppler monitoring to predict fluid responsiveness during surgery.

BACKGROUND: The objective of this study was to test whether non-invasive assessment of respiratory stroke volume variation (ΔrespSV) by oesophageal Doppler monitoring (ODM) can predict fluid responsiveness during surgery in a mixed population. The predictive value of ΔrespSV was evaluated using a grey zone approach. METHODS: Ninety patients monitored using ODM who required i.v. fluids to expand their circulating volume during surgery under general anaesthesia were studied. Patients with a preoperative arrhythmia, right ventricular failure, frequent ectopic beats, or breathing spontaneously were excluded. Haemodynamic variables and oesophageal Doppler indices [peak velocity (PV), stroke volume (SV), corrected flow time (FTc), cardiac output (CO), ΔrespSV, and respiratory variation of PV (ΔrespPV)] were measured before and after fluid expansion. Responders were defined by a >15% increase in SV after infusion of 500 ml crystalloid solution. RESULTS: SV was increased by ≥15% after 500 ml crystalloid infusion in 53 (59%) of the 90 patients. ΔrespSV predicted fluid responsiveness with an area under the receiver-operating characteristic (AUC) curve of 0.91 [95% confidence interval (95% CI): 0.85-0.97, P<0.0001]. The optimal ΔrespSV cut-off was 14.4% (95% CI: 14.3-14.5%). The grey zone approach identified 12 patients (14%) with a range of ΔrespSV values between 14% and 15%. FTc was not predictive of fluid responsiveness (AUC 0.49, 95% CI: 0.37-0.62, P=0.84). CONCLUSIONS: ΔrespSV predicted fluid responsiveness accurately during surgery over a ΔrespSV range between 14% and 15%. In contrast, FTc did not predict fluid responsiveness.

Platelet activating factor (PAF). A review of its effects, antagonists and possible future clinical implications (Part I).

This review is an attempt to summarise recent data on platelet activating factor (PAF) and PAF antagonists from 1988 to the present. This period saw a burst in research activity focused predominantly on the effect of PAF in various organs. The effect of PAF and its antagonists was further intensively studied in vitro on isolated platelets, leucocytes, macrophages and endothelial cells. From these and earlier data, based on the catastrophe theory of Thom and Zeeman, a new concept on the interaction between PAF and various cytokines could be recognised as an important mechanism of action of the phospholipid mediator, suggesting the existence of an autocatalytic feedback network through which PAF can influence cellular function under certain pathophysiological conditions. This mechanism can be regarded as the culmination of our recent knowledge on the role of PAF, and may influence the possible clinical implications of PAF antagonists in the near future. It is recognised that PAF is released in shock and ischaemic states, and that PAF antagonists can protect the heart and brain against ischaemic injury. Therefore, in contrast to the previous period, which was predominantly devoted to the elucidation of the role of PAF in immediate hypersensitivity reactions, studies performed on cerebral, myocardial and intestinal ischaemia as well as in various shock conditions have concentrated on entirely new aspects of the effect of PAF antagonists, emphasising the significance of the inflammatory process and cell-to-cell interactions in these pathophysiological states. This has led to a re-evaluation of the experimental data previously accumulated. At the same time, these new trends in PAF and PAF antagonist research have explored further possibilities for the application of PAF antagonists in clinical practice. Attention has been focused on the physiological role of PAF as a signal molecule, especially between the neuroendocrine system and related sensory organs. The recognition of the significance of PAF in mammalian reproduction is fascinating and may lead to new clinical applications of PAF antagonists. It appears probable that, like eicosanoids, PAF is involved in a great variety of membrane-dependent processes that play a fundamental role in the maintenance of homeostasis. PAF research has provided several potent natural and synthetic antagonists which may facilitate the clinical application of these drugs in the near future.

Efficacy and tolerance of cicletanine, a new antihypertensive agent: overview of 1226 treated patients.

The data gathered from 1226 patients for 20 controlled therapeutic studies performed during the phase-III development of cicletanine, a new antihypertensive agent, were pooled in a computerized database. An extensive statistical analysis of these data collected over 1-2 years was performed to give a clear interpretation of long-term efficacy and tolerance of this drug. In mild to moderate hypertension, the dose-response relationship observed after one month of treatment on diastolic (DBP) and systolic (SBP) blood pressure disappeared during the third month. After a 3-month treatment in monotherapy with the recommended dosage (50-100 mg/day) we observed a mean decrease of 29.7 +/- 17.8 mmHg for SBP and 23.3 +/- 13.2 mmHg for DBP. At this stage 70.9% of patients were stabilized (SBP less than 160 mmHg and DBP less than 95 mmHg) with cicletanine. After this initial regular decrease of blood pressure values, an additional decrease of several mmHg was observed during the 24 months of treatment, thus significantly augmenting the number of stabilized patients. No significant difference in efficacy was observed in adult and elderly (65 to 95 years) patients. The clinical tolerance was very good, only a few slight and transitory side-effects have been reported. Biological tolerance was also very good. Depending on the dosage used, only a slight and transitory variation in sodium and potassium levels was observed. Glucose, creatinine and lipids either remained stable or were improved during treatment. This analysis demonstrates the beneficial effect and the good tolerance of cicletanine (50-100 mg/day) in the treatment of hypertension, which can be explained by its special mode of action.

Study of the effects of cicletanine on the renin-angiotensin-aldosterone system.

The effect of a single dose of 50 mg of cicletanine on plasma renin activity, plasma potassium and aldosterone, blood pressure, urinary volume and sodium and potassium excretion was compared to the effect of the same dose given for 9 days in eight normal volunteers in metabolic balance on 120-140 mEq of sodium and 50-70 mEq potassium. Following 4 days of this standardized diet, the normal volunteers received their first dose of cicletanine after an overnight fast and blood was collected at 30 min, 2, 4 and 6 h for plasma renin activity and aldosterone. Urine excreted following a modest water load was also collected and analysed over a 6-h period. Following the single dose there was an increase in PRA at 1 and 2 h, while there was no such increase with chronic administration. Plasma aldosterone, however, showed no difference between acute and chronic administration of cicletanine treatment. Also plasma uric acid levels increased with acute but not chronic cicletanine. There were no differences in heart rate and blood pressure responses, nor in urine volume, urinary sodium or potassium excretion, or plasma potassium between the different treatments. This study strongly suggests that the antihypertensive effect of cicletanine is not the result of an increased diuresis, as in this case enhanced urinary electrolyte excretion and increased plasma renin activity and aldosterone would be mandatory following chronic administration. Recent evidence suggests that the dissociation between plasma renin activity and aldosterone is the consequence of an effect of cicletanine on intracellular calcium mobilization. This mode of action would explain both the antihypertensive as well as the aldosterone secretion reducing effect of cicletanine.

Review of three studies to determine the efficacy and tolerance of cicletanine in the short- and long-term treatment of essential hypertension.

A double-blind multicentre study was performed initially to assess the effect of 4 weeks' treatment of cicletanine in daily doses of 12.5, 25, 50 and 100 mg, for the treatment of 60 patients with mild to moderate essential hypertension. A significant reduction in blood pressure was achieved with each dosage. Analysis of the responder rate indicated a significant dose-response relationship which was clinically relevant only for the 50 and 100 mg doses. The minimum therapeutic dosage of cicletanine for the treatment of essential hypertension was concluded to be 50 mg daily. A further 12-week study was performed in 40 patients with mild to moderate essential hypertension, commencing with a daily dose of cicletanine (50 mg) and increasing the dosage if necessary to 100 mg and 200 mg daily after 4 and 8 weeks, respectively. Blood pressure control was achieved in all patients and in the majority (70%) with a daily dosage of 100 mg cicletanine. Treatment was continued in all patients until a total duration of 2 years had been completed. Cicletanine was shown to be very well tolerated and a significant reduction in blood pressure was achieved at 6, 9, 12, 18 and 24 months. During the second year of treatment, all the patients were stabilized with a daily dosage of 50 mg cicletanine. These results are consistent with a previously reported study in 25 patients with mild to moderate essential hypertension. Twelve weeks of treatment with cicletanine (50 mg daily) produced a significantly greater reduction in blood pressure than a combination of 5 mg amiloride hydrochloride and 50 mg hydrochlorothiazide daily. This reduction was more significant for the diastolic than the systolic blood pressure measurements. A diastolic blood pressure of 90 mmHg, or less, was achieved in all patients receiving treatment with cicletanine (50 mg daily), except for two patients where the dosage was increased to 100 mg daily.

Effect of Ginkgo biloba extract on microsomal enzyme induction.

Twenty-four healthy volunteers were divided in three groups who were randomly assigned different treatments for 13 days: group I received 400 mg/day of a defined Ginkgo biloba extract (GBE), group II 300 mg/day of phenytoin and group III a placebo. The elimination half-life of antipyrine was measured with a high performance liquid chromatographic technique initially and on the last day of the administration of the treatments. The results show that the half-life of antipyrine was not affected by GBE and placebo treatments, whereas it was significantly decreased (p less than 0.05) frm 12.2 to 6.8 h after phenytoin control treatment. This study demonstrates that GBE has no effect on the hepatic microsomal drug oxidation system.

[Development of an antihypertensive agent. Methodology and cost]. / Développement d'un anti-hypertenseur. Méthodologie et coût.

This schematic analysis demonstrates the great increase in the cost and time required to develop a new molecule, factors which therefore limit the development of new therapeutic methods. The patent period is shorter so that the period of commercialisation of a product by a single drug company is more and more limited. Therefore the situation may occur where the costs of development will no longer be covered. (In addition, the costs of research not leading to a marketable product have not been taken into account).

[Pilot study of Ginkgolide B, a PAF-acether specific inhibitor in the treatment of acute outbreaks of multiple sclerosis]. / Etude pilote d'un inhibiteur spécifique du PAF-acéther, le ginkgolide B dans le traitement des poussées aiguës de sclérose en plaques.

Ten patients with relapsing-remitting multiple sclerosis in acute relapse were treated with a five-day course of intravenous ginkgolide B, a specific inhibitor of PAF-acether. Eight patients had improvement of their neurological score, beginning 2 to 6 days after the initiation of therapy. This improvement was sustained in 5 patients and only transient in 3. Two out of these 3 patients with secondary failure and the other 2 who did not respond to ginkgolide therapy, received i.v. methylprednisolone. Three patients experienced mild side effects under ginkgolide therapy but none of the patients had any serious adverse effect. A controlled randomized study is underway, in order to confirm these results and test higher dosages and more prolonged administration.