Weike Tao

Correction of blood pH attenuates changes in hemodynamics and organ blood flow during permissive hypercapnia

OBJECTIVES To determine whether changes in cardiac output, regional blood flow, and intracranial pressure during permissive hypercapnia are blood pH-dependent and can be attenuated by correction of intravascular acidemia. DESIGN Prospective, controlled study. SETTING Research laboratory. SUBJECTS Female Marino ewes. INTERVENTIONS Animals were instrumented with a pulmonary artery catheter, femoral arterial and venous catheters, a catheter in the third cerebral ventricle, and ultrasonic flow probes on the left carotid, superior mesenteric, and left renal arteries 1 wk before experimentation. At initiation of the protocol, ewes underwent endotracheal intubation and mechanical ventilation under general anesthesia. Minute ventilation was reduced to induce hypercapnia with a target PaCO2 of 80 torr (10.7 kPa). In the pH-uncorrected group (n = 6), arterial blood pH was allowed to decreased without treatment. In the pH-corrected group (n = 5), 14.4 mEq/kg of sodium bicarbonate was given intravenously as a bolus to correct arterial blood pH toward a target arterial pH of 7.40 (dose calculated by the Henderson-Hasselbalch equation). MEASUREMENTS AND MAIN RESULTS Arterial blood pH, PCO2, cardiac output, intracranial pressure, and carotid, superior mesenteric, and renal artery blood flow rates were measured at normocapnic baseline and at every hour during hypercapnia for 6 hrs. In the pH-uncorrected group, arterial blood pH decreased from 7.41 +/- 0.03 at normocapnia to 7.14 +/- 0.01 (p < .01 vs. normocapnia) as blood PCO2 increased to 81.2 +/- 1.8 torr (10.8 +/- 0.2 kPa). In the pH-corrected group, arterial blood pH was 7.42 +/- 0.02 at normocapnia and was maintained at 7.37 +/- 0.01 while PaCO2 was increased to 80.3 +/- 0.9 torr (10.7 +/- 0.1 kPa). Significant increases in cardiac output occurred with the initiation of hypercapnia for both groups (pH-uncorrected group: 4.3 +/- 0.6 L/min at normocapnia vs. 6.8 +/- 1.0 L/min at 1 hr [p < .05]; pH-corrected group: 4.1 +/- 0.4 at normocapnia vs. 5.7 +/- 0.4 L/min at 1 hr [p < .05]). However, this increase was sustained only in the uncorrected group. Changes in carotid and mesenteric artery blood flow rates, as a percent of baseline values, showed sustained significant increases in the pH-uncorrected groups (p < .05) and only transient (carotid at 1 hr) or no (superior mesenteric) significant change in the pH-corrected groups. Conversely, significant increases in renal artery blood flow were seen only in the pH-uncorrected group during the last 2 hrs of the experiment (p < .05). Organ blood flow, as a percent of cardiac output, did not change significantly in either group. Intracranial pressure increased significantly in the pH-uncorrected group (9.0 +/- 1.5 mm Hg at normocapnia vs. 26.8 +/- 5.1 at 1 hr, p < .05), and remained increased, while showing no significant change in the pH-corrected group (8.5 +/- 1.6 mm Hg at normocapnia to 7.7 +/- 4.2 at 1 hr). CONCLUSIONS Acute hypercapnia, induced within 1 hr, is associated with significant increases in cardiac output, organ blood flow, and intracranial pressure. These changes can be significantly attenuated by correction of blood pH with the administration of sodium bicarbonate, without adverse effects on hemodynamics.

Hemodynamic and cardiac contractile function during sepsis caused by cecal ligation and puncture in mice

Sepsis is among the leading causes of death in the critically ill, yet the pathophysiology of sepsis is incompletely understood. Genetically engineered mice offer a unique opportunity to explore the cellular and molecular pathogenesis of sepsis. However, the hemodynamic responses of mice during sepsis are not completely understood because of the difficulty in performing cardiovascular measurements in mice. We used a 1.4-F pressure and conductance catheter to measure hemodynamics in wild-type C57BL/6J mice during sepsis caused by cecal ligation and puncture. Septic mice exhibited significant hypothermia compared with the sham group. In addition, there was a progressive decrease in mean arterial blood pressure and systemic vascular resistance in septic mice as well as an increase in stroke volume and cardiac output. Sepsis also caused a significant time-dependent impairment of left ventricular function as indicated by decreased dp/dtmax and dp/dtmin. The slope of end systolic pressure volume relationship also decreased over time, as did the time varying maximum elastance and preload-recruitable stroke work of the left ventricle. In conclusion, septic mice exhibit hemodynamic alterations during sepsis that are similar to those observed in humans. The miniaturized conductance catheter allows for effective measurements of hemodynamic function in septic mice and provides measurements that cannot be obtained using other cardiovascular monitoring techniques.

Significant reduction in minute ventilation and peak inspiratory pressures with arteriovenous CO2 removal during severe respiratory failure

OBJECTIVES To quantify CO2 removal using an extracorporeal low-resistance membrane gas exchanger placed in an arteriovenous shunt and evaluate its effects on the reduction of ventilatory volumes and airway pressures during severe respiratory failure induced by smoke inhalation injury. DESIGN Prospective study. SETTING Research laboratory. SUBJECTS Adult female sheep (n = 5). INTERVENTIONS Animals were instrumented with femoral and pulmonary arterial catheters and underwent an LD50 cotton smoke inhalation injury via a tracheostomy under halothane anesthesia. Twenty-four hours after smoke inhalation injury, the animals were reanesthetized and systemically heparinized for cannulation of the left carotid and common jugular vein to construct a simple arteriovenous shunt. A membrane gas exchanger was interposed within the arteriovenous shunt, and blood flow produced by the arteriovenous pressure gradient was unrestricted at the time of complete recovery from anesthesia. CO2 removal by the gas exchanger was measured as the product of the sweep gas flow (FIO2 of 1.0 at 2.5 to 3.0 L/min) and the exhaust CO2 content measured with an inline capnometer. CO2 removed by the animals lungs was determined by the expired gas CO2 content in a Douglas bag. We made stepwise, 20% reductions in ventilator support hourly. We first reduced the tidal volume to achieve a peak inspiratory pressure of < 30 cm H2O, and then we reduced the respiratory rate while maintaining normocapnia. PaO2 was maintained by adjusting the FIO2 and the level of positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS Mean blood flow through the arteriovenous shunt ranged from 1154 +/- 82 mL/min (25% cardiac output) to 1277 +/- 38 mL/min (29% cardiac output) over the 6-hr study period. The pressure gradient across the gas exchanger was always < 10 mm Hg. Maximum arteriovenous CO2 removal was 102.0 +/- 9.5 mL/min (96% of total CO2 production), allowing minute ventilation to be reduced from 10.3 +/- 1.4 L/min (baseline) to 0.5 +/- 0.0 L/min at 6 hrs of arteriovenous CO2 removal while maintaining normocapnia. Similarly, peak inspiratory pressure decreased from 40.8 +/- 2.1 to 19.7 +/- 7.5 cm H2O. PaO2 was maintained at > 100 torr (> 13.3 kPa) at maximally reduced ventilator support. Mean arterial pressure and cardiac output did not change significantly as a result of arteriovenous shunting. CONCLUSIONS Extracorporeal CO2 removal using a low-resistance gas exchanger in a simple arteriovenous shunt allows significant reduction in minute ventilation and peak inspiratory pressure without hypercapnia or the complex circuitry and monitoring required for conventional extracorporeal membrane oxygenation. Arteriovenous CO2 removal can be applied as an easy and cost-effective treatment to minimize ventilator-induced barotrauma and volutrauma during severe respiratory failure.

New clinically relevant sheep model of severe respiratory failure secondary to combined smoke inhalation/cutaneous flame burn injury.

Objectives: To develop a predictable, dose‐dependent, clinically relevant model of severe respiratory failure associated with a 40% total body surface area, full‐thickness (third‐degree) cutaneous flame burn and smoke inhalation injury in adult sheep. Design: Model development. Setting: Research laboratory. Subjects: Adult female sheep (n = 22). Interventions: Animals were divided into three groups, determined by the number of smoke breaths administered (24, 36, 48) for a graded inhalation injury. The smoke was insufflated into a tracheostomy with a modified bee smoker at airway temperatures <40°C. All animals concurrently received a 40% total body surface area (third‐degree) cutaneous flame burn to the body (flanks). After injury, the animals were placed on volume‐controlled ventilation to achieve PaO2 >60 mm Hg and PaCO2 <40 mm Hg. Arterial blood gases and ventilator settings were monitored every 6 hrs postinjury for up to 7 days. Measurements and Main Results: All animals survived the induction of injury. In the 24 smoke breath/40% total body surface area burn (24/40) group, PaO2/FIO2 never decreased below 300, and peak inspiratory pressure was consistently <14 cm H2O with normal arterial blood gases throughout the observation period. With 36 smoke breaths/40% total body surface area burn (36/40) (n = 7), all animals had PaO2/FIO2 of <200 and peak inspiratory pressure of 26 cm H2O within 40‐48 hrs, as 30% died during the study period. With 48 smoke breaths/40% total body surface area burn (48/40) (n = 12), all animals developed respiratory distress syndrome (RDS) in 24‐30 hrs, but none survived the experimental period. Conclusions: Development of RDS by smoke and cutaneous flame burn injury depends on smoke inhalation dose. A combination of 36 breaths of smoke and a 40% total body surface area (third‐degree) cutaneous flame burn injury can induce severe RDS (PaO2/FIO2 <200) within 40‐48 hrs to allow evaluation of various treatment modalities of RDS.

Total Arteriovenous CO2 Removal: Simplifying Extracorporeal Support for Respiratory Failure

BACKGROUND To reduce the complexity, complications, and cost of conventional extracorporeal membrane oxygenation, we have developed a technique of simplified arteriovenous extracorporeal CO2 removal (AVCO2R) with a low-resistance membrane gas exchanger for total CO2 removal to provide lung rest in the setting of severe respiratory failure. METHODS We initially used AVCO2R in healthy animals to quantify the gas exchange capabilities of the system and establish ventilator management protocols for the subsequent studies of AVCO2R in a large animal model of respiratory failure secondary to a severe smoke inhalation injury. RESULTS In healthy sheep the maximum spontaneous arteriovenous flow ranged from 1,350 to 1,500 mL/min, whereas CO2 removal plateaued at a blood flow of approximately 1,000 mL/min in which 112 +/- 3 mL/min CO2 was removed, allowing an 84% reduction in the minute ventilation of from 6.9 +/- 0.8 L/min to 1.1 +/- 0.4 L/min (p < 0.01) without triggering hypercapnia. A subsequent reduction in extracorporeal flow at a reduced minute volume led to the development of hypercapnia only if it decreased to less than 500 mL/min. We also applied AVCO2R in mechanically ventilated sheep with a severe smoke inhalation injury and removed 95% (111 +/- 4 mL/min) of the total CO2 production. This allowed the minute ventilation to be reduced by 95% and the peak inspiratory pressures by 52% (both p < 0.05) over 6 hours and produced no adverse hemodynamic effects. The partial pressure of arterial oxygen was maintained above 100 mm Hg at a maximally reduced minute volume. The mean AVCO2R flow was 1,213 +/- 29 mL/min, averaging 27% +/- 1% of the cardiac output. CONCLUSIONS We conclude that AVCO2R in a simple arteriovenous shunt is a less complicated technique than extracorporeal membrane oxygenation and is capable of total CO2 removal that allows a significant reduction in the minute ventilation and peak airway pressure during severe respiratory failure.

Reduced ventilator pressure and improved P/F ratio during percutaneous arteriovenous carbon dioxide removal for severe respiratory failure

OBJECTIVE To evaluate the effect of percutaneous arteriovenous carbon dioxide removal (AVCO2R) on ventilator pressures and P/F ratio in a clinically relevant large-animal model of severe respiratory failure. SUMMARY BACKGROUND DATA AVCO2R was developed as a simple arteriovenous shunt with a commercially available low-resistance gas exchange device of sufficient surface area for near-total CO2 removal. With an AV shunt 10% to 15% of cardiac output, AVCO2R allows a reduction in ventilator airway pressures without hypercapnia or the complex circuitry and monitoring required for conventional ECMO. METHODS AVCO2R was applied to a new, clinically relevant large-animal model of severe respiratory failure created by smoke inhalation and cutaneous flame bum injury. Adult sheep (n = 9, 38+/-6 kg) received a 40% total body surface area, third-deinsufflation. After injury, all animals were placed on volume-controlled mechanical ventilation to achieve PaO2 > 60 mmHg and PacO2 < 40 mmHg. Animals were placed on AVCO2R within 40 to 48 hours of injury when the PaO2/FiO2 was <200. Animals underwent cannulation of the carotid artery and jugular vein with percutaneous 10F arterial and 14F venous cannulas. Shunt flow was continuously monitored using an ultrasonic flow probe and calculated as a percentage of cardiac output. RESULTS AVCO2R flows of 800 to 900 ml/min (11% to 13% cardiac output) achieved 77 to 104 ml/min of CO2 removal (95% to 97% total CO2 production) while maintaining normocapnia. Significant reductions in ventilator settings were tidal volume, 421.3+/-39.8 to 270.0+/-6.3 ml; peak inspiratory pressure, 24.8+/-2.4 to 13.7+/-0.7 cm H2O; minute ventilation, 12.7+/-1.4 to 6.2+/-0.8 L/min; respiratory rate, 25.4+/-1.3 to 18.4+/-1.8 breaths/min; and FiO2, 0.88+/-0.1 to 0.39+/-0.1. The P/F ratio increased from 151.5+/-40.0 at baseline to 320.0+/-17.8 after 72 hours. CONCLUSIONS Percutaneous AVCO2R allows near-total CO2 removal and significant reductions in ventilator pressures with improvement in the P/F ratio.

Prolonged hemodynamic stability during arteriovenous carbon dioxide removal for severe respiratory failure

OBJECTIVE The effects of prolonged arteriovenous carbon dioxide removal on hemodynamics during severe respiratory failure were evaluated in adult sheep with severe smoke inhalation injury. METHODS Adult female sheep (n = 6,33.8 +/- 5.2 kg) were subjected to intratracheal cotton severe smoke insufflation to a mean carboxyhemoglobin level of 83% +/- 3%. Twenty-four hours after injury, a low-resistance 2.5 m2 membrane oxygenator was placed in a carotid-to-jugular pumpless arteriovenous shunt at unrestricted flow to allow complete carbon dioxide removal and reductions in ventilator support. Animals remained conscious, and heart rate, cardiac output, mean arterial pressure, and pulmonary arterial pressure were measured at baseline, after injury, and daily during support with the arteriovenous carbon dioxide removal circuit for 7 days. RESULTS All animals survived the study period. Carbon dioxide removal ranged from 99.7 +/- 13.7 to 152.2 +/- 16.2 ml/min, and five (83%) of the six animals were successfully weaned from the ventilator before day 7. During full support with the arteriovenous carbon dioxide removal circuit, shunt flow ranged from 1.24 +/- 0.06 to 1.43 +/- 0.08 L/min and accounted for 20.1% +/- 1.4% to 25.9% +/- 2.4% of cardiac output. No statistically significant changes in heart rate, cardiac output, mean arterial pressure, or pulmonary artery pressure were demonstrated over the study course despite the extracorporeal shunt flow. CONCLUSIONS Arteriovenous carbon dioxide removal as a simplified means of extracorporeal gas exchange support is relatively safe without adverse hemodynamic effects or complications.

Intravascular membrane oxygenator and carbon dioxide removal devices: A review of performance and improvements

The first intravascular oxygenator and carbon dioxide (CO2) removal device (IVOX), conceived by Mortensen, was capable of removing 30% of CO2 production of an adult at normocapnia with a measurable reduction in ventilator requirements. Through studies of mathematical modeling, an ex vivo venovenous bypass circuit to model the human vena cava, animal models of severe smoke inhalation injury, and patients with acute respiratory failure, the practice of permissive hypercapnia has been established to enhance CO2 removal by IVOX. By allowing the blood pCO2 to rise gradually, the CO2 excretion by IVOX can be linearly increased in a 1:1 relationship. Experimental and clinical studies have shown that CO2 removal by IVOX can increase from 30 to 40 ml/min at a normal blood pCO2 to 80 to 90 ml/min at a pCO2 of 90 mm Hg. In addition, IVOX with permissive hypercapnia allows a significant reduction in minute ventilation and peak airway pressure. Active blood mixing to decrease the boundary layer resistance in the blood can significantly improve O2 transfer by up to 49% and CO2 removal by up to 35%. Design changes can also improve the performance of IVOX. Increased surface area with more fibers and enhanced mixing by increased fiber crimping in new prototypes of IVOX significantly increased CO2 removal. Other groups have used alternative designs to address the limited performance of intravascular gas exchange devices. With improved design and patient management, clinically meaningful gas exchange and reduction in mechanical ventilatory support may be achieved during treatment of severe respiratory failure.

Extracorporeal heparin adsorption following cardiopulmonary bypass with a heparin removal device : An alternative to protamine

OBJECTIVES To evaluate the therapeutic efficacy and applicability of a heparin removal device (HRD) based on plasma separation and poly-L-lysine (PLL) affinity adsorption as an alternative to protamine in reversing systemic heparinization following cardiopulmonary bypass (CPB). DESIGN A prospective study. SETTING University research laboratory. SUBJECTS Adult female swine (n=7). INTERVENTIONS Female Yorkshire swine (n=7, 67.3+/-3.5 [SEM] kg) were subjected to 60 mins of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual-lumen cannula which was connected to an HRD via extracorporeal circulation. Blood flow was drained at 1431.2+/-25.4 mL/min from the inferior vena cava, through the plasma separation chamber of the HRD (where heparin was bound to PLL), and reinfused into the right atrium. The HRD run time was determined by a previously established mathematical model of first-order exponential depletion. MEASUREMENTS AND MAIN RESULTS Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, kaolin and celite activated clotting time (ACT), activated partial thromboplastin time (APTT), heparin concentration, and plasma free hemoglobin were obtained before, during, and after the use of the HRD. Pre-CPB ACT was 167+/-89 secs (kaolin) and 99+/-7 secs (celite), and APTT was 34+/-5 secs. The HRD run time averaged 27.4 +/-1.5 mins targeted to remove 90% total body heparin. Use of the HRD was not associated with any adverse hemodynamic reactions or increases in plasma free hemoglobin. The heparin concentration immediately following CPB was 4.85+/-0.24 units/mL, with ACT >1000 secs and APTT >150 secs in all animals. During heparin removal, total body heparin content followed first-order exponential depletion kinetics. At the end of the HRD run, heparin concentration decreased to 0.51+/-0.09 units/mL, with kaolin ACT returning to 177+/-22 secs, celite ACT returning to 179+/-17 secs, and APTT returning to 27+/-3 secs (p > .05 vs. pre-CPB baseline for all variables). CONCLUSIONS The HRD is capable of reversal of anticoagulation following CPB without significant blood cell damage or changes in hemodynamics. The HRD, therefore, can serve as an alternative to achieve heparin clearance in clinical situations where use of protamine may be contraindicated.

The Dragon Strikes: Lessons from the Wenchuan Earthquake

Guo Chen, MD,* Wei Lai, MD,* Fei Liu, MD,* Qingxiang Mao, MD,† Faping Tu, MD,‡§ Jin Wen, PhD, Hong Xiao, MD,* Jian-cheng Zhang, MD,¶ Tao Zhu, MD,* Bin Chen, MD,‡ Zhao-yang Hu, PhD,* Rong-Mei Li,* Zhi Liang, MD,# Hu Nie, MD,¶ Hong Yan, MD,† Bang-Xiang Yang, MD,* Quan Du, MD,† Wen-Xia Huang,* Yao-wen Jiang, MD,¶ Anne Siu-king Kwan, MD,** Li Song, MD,* Chao-Meng Wu, MD,* Tia Xiang, MD,‡ Hong-wei Xu, MD,* Wayne Bond Lau, MD,†† Hai-Bo Song, MD,* Chuan-Bin Wen, MD,* Zhen-Hai Yao, MD, PhD,‡‡ Lan Zhang, MB,* Jianrong Zeng, MD,§§ Yue-E Dai, MD,* Bernard L. Lopez, MD,** Jian-qiao Zheng, MD,* Jihong Zhou, MD,† Theodore A. Christopher, MD,** Xin L. Ma, MD, PhD,** Hui Yu, MD,* Li-Li Xu, MD,* Qiao Guo, MD,* Zhi-Ping Song, MD,* Ernest Volinn, PhD, King Kryger, PhD, Yu Cao, MD,¶ Hengjiang Ge, MD,† Hui Liu, MD,* Chao-zhi Luo, MD,* Weike Tao, MD,§ Yun-Xia Zuo, MD, PhD,* and Jin Liu, MD*