Ventilation during extracorporeal support : Why and how.

The main target of extracorporeal support is to achieve viable gas exchange, while minimizing the risk of ventilator-induced lung injury, achieved through a decreased mechanical ventilation load on the natural lung. However, during veno-venous extracorporeal membrane oxygenation (ECMO), mechanical ventilation is still necessary in order to prevent lung collapse and/or if extracorporeal blood flow is not sufficient to guarantee adequate gas exchange. In this review, we will summarize the physiology of extracorporeal support and the rationale for continuing mechanical ventilation in this context. Furthermore, we will review the current clinical practice among ECMO centers and their suggestions regarding mechanical ventilator settings. While optimal ventilatory settings are still a matter of debate, the use of a strategy combining low tidal volume and limited inspiratory pressures is accepted worldwide. On the contrary, the choice of applied positive end-expiratory pressure (PEEP) varies between the total rest strategy and open lung strategy. Finally, the use of assisted or spontaneous ventilation will be discussed.

Ventilator-related causes of lung injury: the mechanical power.

PURPOSE: We hypothesized that the ventilator-related causes of lung injury may be unified in a single variable: the mechanical power. We assessed whether the mechanical power measured by the pressure-volume loops can be computed from its components: tidal volume (TV)/driving pressure (∆P aw), flow, positive end-expiratory pressure (PEEP), and respiratory rate (RR). If so, the relative contributions of each variable to the mechanical power can be estimated. METHODS: We computed the mechanical power by multiplying each component of the equation of motion by the variation of volume and RR: [Formula: see text]where ∆V is the tidal volume, ELrs is the elastance of the respiratory system, I:E is the inspiratory-to-expiratory time ratio, and R aw is the airway resistance. In 30 patients with normal lungs and in 50 ARDS patients, mechanical power was computed via the power equation and measured from the dynamic pressure-volume curve at 5 and 15 cmH2O PEEP and 6, 8, 10, and 12 ml/kg TV. We then computed the effects of the individual component variables on the mechanical power. RESULTS: Computed and measured mechanical powers were similar at 5 and 15 cmH2O PEEP both in normal subjects and in ARDS patients (slopes = 0.96, 1.06, 1.01, 1.12 respectively, R (2) > 0.96 and p < 0.0001 for all). The mechanical power increases exponentially with TV, ∆P aw, and flow (exponent = 2) as well as with RR (exponent = 1.4) and linearly with PEEP. CONCLUSIONS: The mechanical power equation may help estimate the contribution of the different ventilator-related causes of lung injury and of their variations. The equation can be easily implemented in every ventilator's software.

Effect of body mass index in acute respiratory distress syndrome.

BACKGROUND: Obesity is associated in healthy subjects with a great reduction in functional residual capacity and with a stiffening of lung and chest wall elastance, which promote alveolar collapse and hypoxaemia. Likewise, obese patients with acute respiratory distress syndrome (ARDS) could present greater derangements of respiratory mechanics than patients of normal weight. METHODS: One hundred and one ARDS patients were enrolled. Partitioned respiratory mechanics and gas exchange were measured at 5 and 15 cm H2O of PEEP with a tidal volume of 6-8 ml kg(-1) of predicted body weight. At 5 and 45 cm H2O of PEEP, two lung computed tomography scans were performed. RESULTS: Patients were divided as follows according to BMI: normal weight (BMI≤25 kg m(-2)), overweight (BMI between 25 and 30 kg m(-2)), and obese (BMI>30 kg m(-2)). Obese, overweight, and normal-weight groups presented a similar lung elastance (median [interquartile range], respectively: 17.7 [14.2-24.8], 20.9 [16.1-30.2], and 20.5 [15.2-23.6] cm H2O litre(-1) at 5 cm H2O of PEEP and 19.3 [15.5-26.3], 21.1 [17.4-29.2], and 17.1 [13.4-20.4] cm H2O litre(-1) at 15 cm H2O of PEEP) and chest elastance (respectively: 4.9 [3.1-8.8], 5.9 [3.8-8.7], and 7.8 [3.9-9.8] cm H2O litre(-1) at 5 cm H2O of PEEP and 6.5 [4.5-9.6], 6.6 [4.2-9.2], and 4.9 [2.4-7.6] cm H2O litre(-1) at 15 cm H2O of PEEP). Lung recruitability was not affected by the body weight (15.6 [6.3-23.4], 15.7 [9.8-22.2], and 11.3 [6.2-15.6]% for normal-weight, overweight, and obese groups, respectively). Lung gas volume was significantly lower whereas total superimposed pressure was significantly higher in the obese compared with the normal-weight group (1148 [680-1815] vs 827 [686-1213] ml and 17.4 [15.8-19.3] vs 19.3 [18.6-21.7] cm H2O, respectively). CONCLUSIONS: Obese ARDS patients do not present higher chest wall elastance and lung recruitability.

Friday night ventilation: a safety starting tool kit for mechanically ventilated patients.

We wish to report here a practical approach to an acute respiratory distress syndrome (ARDS) patient as devised by a group of intensivists with different expertise. The referral scenario is an intensive care unit of a Community Hospital with limited technology, where a young doctor, alone, must deal with this complicate syndrome during the night. The knowledge of pulse oximetry at room air and at 100% oxygen allows to estimate the PaO2 and the cause of hypoxemia, shunt vs. VA/Q maldistribution. The ARDS severity (mild [200

Time to reach a new steady state after changes of positive end expiratory pressure.

PURPOSE: To assess the time interval required to reach a new steady state of oxygenation-, ventilation-, respiratory mechanics- and hemodynamics-related variables after decreasing/increasing positive end expiratory pressure (PEEP). METHODS: In 23 patients (group 1) with acute respiratory distress syndrome (ARDS), PEEP was decreased from 10 to 5 cmH2O and, after 60', it was increased from 5 to 15 cmH2O. In 21 other ARDS patients (group 2), PEEP was increased from 10 to 15 cmH2O and, after 60', decreased from 15 to 5 cmH2O. Oxygenation, ventilation, respiratory mechanics and hemodynamic variables were recorded at time 5', 15', 30' and 60' after each PEEP change. RESULTS: When PEEP was decreased, PaO2, PaO2/FiO2, venous admixture and arterial oxygen saturation reached their equilibrium after 5'. In contrast, when PEEP was increased, the equilibrium was not reached even after 60'. The ventilation-related variables did not change significantly with PEEP. The respiratory system compliance, when PEEP was decreased, significantly worsened only after 60'. Hemodynamics did not change significantly with PEEP. In the individual patients the change of oxygenation-related variables and of respiratory system compliance observed after 5' could predict the changes recorded after 60'. This was not possible for PaCO2. CONCLUSIONS: We could not find a unique equilibration time for all the considered variables. However, in general, a decremental PEEP test requires far lower equilibrium time than an incremental PEEP test, suggesting a different time course for derecruitment and recruitment patterns.

In vivo conditioning of acid-base equilibrium by crystalloid solutions: an experimental study on pigs.

PURPOSE: Large infusion of crystalloids may induce acid-base alterations according to their strong ion difference ([SID]). We wanted to prove in vivo, at constant PCO(2), that if the [SID] of the infused crystalloid is equal to baseline plasma bicarbonate, the arterial pH remains unchanged, if lower it decreases, and if higher it increases. METHODS: In 12 pigs, anesthetized and mechanically ventilated at PCO(2) ≈40 mmHg, 2.2 l of crystalloids with a [SID] similar to (lactated Ringer's 28.3 mEq/l), lower than (normal saline 0 mEq/l), and greater than (rehydrating III 55 mEq/l) baseline bicarbonate (29.22 ± 2.72 mEq/l) were infused for 120 min in randomized sequence. Four hours of wash-out were allowed between the infusions. Every 30 min up to minute 120 we measured blood gases, plasma electrolytes, urinary volume, pH, and electrolytes. Albumin, hemoglobin, and phosphates were measured at time 0 and 120 min. RESULTS: Lactated Ringer's maintained arterial pH unchanged (from 7.47 ± 0.06 to 7.47 ± 0.03) despite a plasma dilution around 12%. Normal saline caused a reduction in pH (from 7.49 ± 0.03 to 7.42 ± 0.04) and rehydrating III induced an increase in pH (from 7.46 ± 0.05 to 7.49 ± 0.04). The kidney reacted to the infusion, minimizing the acid-base alterations, by increasing/decreasing the urinary anion gap, primarily by changing sodium and chloride concentrations. Lower urine volume after normal saline infusion was possibly due to its greater osmolarity and chloride concentration as compared to the other solutions. CONCLUSIONS: Results support the hypothesis that at constant PCO(2), pH changes are predictable from the difference between the [SID] of the infused solution and baseline plasma bicarbonate concentration.

The rule regulating pH changes during crystalloid infusion.

PURPOSE: To define the rule according to which crystalloid solutions characterized by different strong ion difference (SID) modify the acid-base variables of human plasma. METHODS: With a previously validated software, we computed the effects of diluting human plasma with crystalloid solutions ([SID] 0-60, 10 mEq/l stepwise). An equation was derived to compute the diluent [SID] required to maintain the baseline pH unchanged, at constant PCO2 and at every dilution fraction. The results were experimentally tested using fresh frozen plasma, re-warmed at 37°C, equilibrated at PCO2 35 and 78 mmHg, at baseline and after the infusion of crystalloid solutions with 0, 12, 24, 36, 48 mEq/l [SID]. RESULTS: The mathematical analysis showed that the diluent [SID] required to maintain unmodified the baseline pH equals the baseline bicarbonate concentration, [HCO3⁻], assuming constant PCO2 throughout the process. The experimental data confirmed the theoretical analysis. In fact, at the baseline [HCO3⁻] of 18.3 ± 0.3 mmol/l (PCO2 35 mmHg) the pH was 7.332 ± 0.004 and remained 7.333 ± 0.003 when the diluting [SID] was 18.5 ± 0.0 mEq/l. At baseline [HCO3⁻] of 19.5 ± 0.3 mmol/l (PCO2 78 mmHg) the pH was 7.010 ± 0.003 and remained 7.004 ± 0.003 when the diluting [SID] was 19.1 ± 0.1 mEq/l. At both PCO2 values infusion with [SID] lower or greater than baseline [HCO3⁻] led pH to decrease or increase, respectively. CONCLUSIONS: The baseline [HCO3⁻] dictates the pH response to crystalloid infusion. If a crystalloid [SID] equals baseline [HCO3⁻], pH remains unchanged at constant PCO2, whereas it increases or decreases if the [SID] is greater or lower, respectively.

Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis.

Prone positioning has been used for over 30 years in the management of patients with acute respiratory distress syndrome (ARDS). This maneuver has consistently proven capable of improving oxygenation in patients with acute respiratory failure. Several mechanisms can explain this observation, including possible intervening net recruitment and more homogeneously distributed alveolar inflation. It is also progressively becoming clear that prone positioning may reduce the nonphysiological stress and strain associated with mechanical ventilation, thus decreasing the risk of ventilator-induced lung injury, which is known to adversely impact patient survival. The available randomized clinical trials, however, have failed to demonstrate that prone positioning improves the outcomes of patients with ARDS overall. In contrast, the individual patient meta-analysis of the four major clinical trials available clearly shows that with prone positioning, the absolute mortality of severely hypoxemic ARDS patients may be reduced by approximately 10%. On the other hand, all data suggest that long-term prone positioning may expose patients with less severe ARDS to unnecessary complications.

Dilutional acidosis: where do the protons come from?

PURPOSE: To investigate the mechanism of acidosis developing after saline infusion (dilutional acidosis or hyperchloremic acidosis). METHODS: We simulated normal extracellular fluid dilution by infusing distilled water, normal saline and lactated Ringer's solution. Simulations were performed either in a closed system or in a system open to alveolar gases using software based on the standard laws of mass action and mass conservation. In vitro experiments diluting human plasma were performed to validate the model. RESULTS: In our computerized model with constant pKs, diluting extracellular fluid modeled as a closed system with distilled water, normal saline or lactated Ringer's solution is not associated with any pH modification, since all its determinants (strong ion difference, CO(2) content and weak acid concentration) decrease at the same degree, maintaining their relative proportions unchanged. Experimental data confirmed the simulation results for normal saline and lactated Ringer's solution, whereas distilled water dilution caused pH to increase. This is due to the increase of carbonic pK induced by the dramatic decrease of ionic strength. Acidosis developed only when the system was open to gases due to the increased CO(2) content, both in its dissociated (bicarbonate) and undissociated form (dissolved CO(2)). CONCLUSIONS: The increase in proton concentration observed after dilution of the extracellular system derives from the reaction of CO(2) hydration, which occurs only when the system is open to the gases. Both Stewart's approach and the traditional approach may account for these results.

Effects of volume shift on the pressure-volume curve of the respiratory system in ALI/ARDS patients.

AIM: The pressure-volume (PV) curve in acute lung injury and acute respiratory distress syndrome (ALI/ARDS) patients has been proposed for estimating the underlying pathology, lung recruitment and setting mechanical ventilation. The supersyringe method may lead to artifacts due to thermodynamics and gas exchange. Another possible confounding factor is the volume shift, primarily blood, out of the chest wall when the intrathoracic pressures rise. We set out to quantify the volume shift and investigate its mechanisms. METHODS: Ten ALI/ARDS patients (5 males/5 females, PaO(2)/FiO(2) 222+/-67) were studied in the Intensive Care Unit, University Hospital. PV curve was performed by a supersyringe (0.100 L, 14 steps Delta-Vgas) while recording the chest wall volume difference (Delta-Vcw) by the optoelectronic plethysmography. Differences in airway (Delta-Paw) and esophageal (Delta-Pes) pressures were measured during the maneuver. Volume shift was defined as Delta-Vcw-Delta-Vgas, corrected for thermodynamic and gas exchange. RESULTS: Starting compliance (P<0.05), inflation/deflation compliance (P<0.01), hysteresis (P<0.01) and unrecovered volume (P<0.01) were significantly affected by volume shift. The volume shift was directly correlated to the product Delta-Paw*inflation time (R2=0.87, P<0.001), to the ratio of Delta-Pes to Delta-Paw (R2=0.80, P<0.01) and to central venous pressure (R2=0.42, P<0.05) and inversely correlated with the deflation time (R2=0.58, P<0.05). At 20 cmH2O of airway pressure the volume shift between the inflation and deflation limbs of the PV curve amounted to 0.099+/-0.058 L. CONCLUSIONS: The volume shift, constituted mainly of blood, significantly affects both inspiratory and expiratory PV curve. Caution is needed when interpreting the PV parameters (Minerva Anestesiol 2007;73:1-10).

Gastric tonometry.

Gastric tonometry was originally proposed to assess the splanchnic perfusion. Several technological improvements have been introduced over the years and, to date, the preferred way to estimate the splanchnic perfusion is to rely on the arterial-gastric PCO2 gap. In this brief review we will discuss the value of the gastric tonometry, its physiological background and the clinical results observed so far.

Respiratory acidosis: is the correction with bicarbonate worth?

Bicarbonate infusion is traditionally used to increase pH during metabolic acidosis, but it has been also suggested to increase the pH during permissive hypercapnia. In this paper we will discuss the physicochemical effect of adding (Na+ HCO3-), first in a closed system (venous blood) and then in an open system (the blood after the lung). According to Stewart model, in the closed system two independent variables are changed (CO2 and strong ion difference). As a first result changes in pH are negligible. If the CO2 is cleared by the lung and the PCO2 is maintained as before the infusion, the rise in pH is due to the SID increase caused by the (Na+) rise. The effect is independent on (HCO3-) infusion and equivalent to adding (Na+ OH-) instead of (Na+ HCO3-).

Physical and biological triggers of ventilator-induced lung injury and its prevention.

Ventilator-induced lung injury is a side-effect of mechanical ventilation. Its prevention or attenuation implies knowledge of the sequence of events that lead from mechanical stress to lung inflammation and stress at rupture. A literature review was undertaken which focused on the link between the mechanical forces in the diseased lung and the resulting inflammation/rupture. The distending force of the lung is the transpulmonary pressure. This applied force, in a homogeneous lung, is shared equally by each fibre of the lung's fibrous skeleton. In a nonhomogeneous lung, the collapsed or consolidated regions do not strain, whereas the neighbouring fibres experience excessive strain. Indeed, if the global applied force is excessive, or the fibres near the diseased regions experience excessive stress/strain, biological activation and/or mechanical rupture are observed. Excessive strain activates macrophages and epithelial cells to produce interleukin-8. This cytokine recruits neutrophils, with consequent full-blown inflammation. In order to prevent initiation of ventilator-induced lung injury, transpulmonary pressure must be kept within the physiological range. The prone position may attenuate ventilator-induced lung injury by increasing the homogeneity of transpulmonary pressure distribution. Positive end-expiratory pressure may prevent ventilator-induced lung injury by keeping open the lung, thus reducing the regional stress/strain maldistribution. If the transpulmonary pressure rather than the tidal volume per kilogram of body weight is taken into account, the contradictory results of the randomised trials dealing with different strategies of mechanical ventilation may be better understood.

Sepsis: state of the art.

In recent years, we have considerably widened our knowledge of the pathophysiology of sepsis and some procedures, aiming both to relieve symptoms and control the inflammation/coagulation reaction, have proven to be effective in increasing survival. This improves when mechanical ventilation is applied with low tidal volumes, fluid replacement and the use of cardioactive drugs are titrated on the oxygen saturation of hemoglobin in the central venous system and blood glucose does not exceed certain limits. It is also evident that inflammation and coagulation are closely related to each other. The inhibition of only one pathway, such as the inhibition of inflammation with high dosage steroids or the inhibition of coagulation with antithrombin, does not produce a survival improvement. The only molecule which has proven to be notably effective in reducing mortality is Activated Protein C interacting on coagulation/fibrinolysis, as well as on inflammation processes. Multinodal modulation of several interdependent processes may be the probable reason for the proven effectiveness of this treatment.

Estimation of end-expiratory lung volume variations by optoelectronic plethysmography.

OBJECTIVE: To test the capability of optoelectronic plethysmography (OEP) to monitor positive end-expiratory pressure (PEEP)-induced changes of end-expiratory lung volume (EELV) changes in mechanically ventilated paralyzed patients. DESIGN: Laboratory and clinical investigation. SETTING: Intensive care unit of the Ospedale Maggiore Policlinico di Milano. PATIENTS: A total of eight patients with respiratory failure of various degrees, sedated and paralyzed. INTERVENTIONS: PEEP variations (+/-5 cm H2O) relative to the baseline PEEP of 10 cm H2O. MEASUREMENTS AND MAIN RESULTS: In the model protocol, we tested the reproducibility of the OEP by repeating volume measurements of a plastic torso model over a 21-hr period, every 30 mins. The variations of OEP measurements of the torso model (9337 mL value) were encountered in a range of 16 mL (sd = 4 mL). In the patient protocol, we measured the end-expiratory volume of the chest wall (EEVCW) breath-by-breath by OEP before, during, and after the PEEP increase/decrease and we compared its variations with the corresponding variations of EELV measured by helium dilution technique. The regression line between EELV changes measured by helium and EEVCW changes measured by OEP resulted very close to the identity line (slope 1.06, intercept -0.02 L, r(2) = 0.89) and their difference was not related to their absolute magnitude. After PEEP increase, the new steady state of EEVCW was reached approximately in 15 breaths; and, after PEEP decrease, in 3-4 breaths. The slow increase in EEVCW was mainly because of the abdominal compartment. CONCLUSION: OEP measurements of EEVCW accurately reflect the changes of EELV. Furthermore, OEP allows a continuous compartmental analysis, even during unsteady conditions.