Airway Pressure Release Ventilation: A Pediatric Case Series

Pediatric Pulmonology 42:83 88 (2007) Case Reports Airway Pressure Release Ventilation: A Pediatric Case Series Jambunathan Krishnan, MD 1 * and Wynne Morrison, MD 2 Summary. Airway pressure release ventilation (APRV) is a relatively new mode of mechanical ventilation (MV) first described in animal studies in 1987 and in humans in 1988. It is a timetriggered, time-cycled, pressure-limited mode where a high level of continuous positive airway pressure (CPAP) is maintained with brief regular releases in pressure, and spontaneous breathing is allowed throughout the cycle. In theory, it is consistent with a lung protective approach while having some hypothetical advantages over HFOV. The use of this mode of ventilation in pediatrics has been limited. The authors describe their experience with this mode of ventilation in a series of pediatric patients. Pediatr Pulmonol. 2007; 42:83 88. ß 2006 Wiley-Liss, Inc. Key words: pediatric; ARDS; airway pressure release ventilation; mechanical ventilation. INTRODUCTION Airway pressure release ventilation (APRV) is a relatively new mode of mechanical ventilation (MV) first described in animal studies in 1987 1 and in humans in 1988. 2 It is a time-triggered, time-cycled, pressure-limited mode: a high level of continuous positive airway pressure (CPAP) is maintained with brief regular releases in pressure, and spontaneous breathing is allowed throughout the cycle (Fig. 1). 3 Clinical trials with the APRV mode of ventilation have been conducted almost exclusively in adults, with only a few pediatric reports in the literature. 4,5 We describe a series of seven pediatric patients managed with APRV. This retrospective review was approved by the Institutional Review Board of the University of Maryland. CASE REPORTS Case 1 A 9-year-old male with leukemia presented with septic shock, Acute Respiratory Distress Syndrome (ARDS), and multiorgan dysfunction. He became progressively hypoxemic (oxygenation index (OI) ¼ 26.3) on pressure control (PC) ventilation despite the following settings (all conventional settings reported are on the Siemens Servo 300 or Servo i ): fraction of inspired oxygen (FiO 2 ) ¼ 1.0, SIMV PC with peak inspiratory pressure (PIP) ¼ 38 cm H 2 O, positive end-expiratory pressure (PEEP) ¼ 14 cm H 2 O. He had a mean airway pressure (P aw )of24cmh 2 O. His PaO 2 was 91 mm Hg. High frequency oscillatory ß 2006 Wiley-Liss, Inc. ventilation (HFOV) was unsuccessful due to hypotension unresponsive to fluid administration and vasopressors. Initial APRV settings were P High 37 cm H 2 OP Low 0cm H 2 OT High 4 sec T Low 0.5 sec. Oxygenation improved over 84 hr and his OI improved to 10.7 (P aw 32 cm H 2 O, PaO 2 178 mm Hg) on settings of P High 33 cm H 2 OP Low 0cm H 2 OT High 5 T Low 0.5 FiO 2 0.6. He did not require neuromuscular blockade (NMB) on APRV. He eventually weaned off MV and was discharged home. Case 2 The same patient returned a few months later with recurrent septic shock and ARDS. When he required PC settings of PIP, PEEP, P aw, and FiO 2 of 38 cm H 2 O, 14 cm H 2 O, 24 cm H 2 O, and 0.6, the team again chose to use 1 Cardinal Glennon Childrens Medical Center, St. Louis University, Pediatric Critical Care, St. Louis, Missouri. 2 Childrens Hospital of Philadelphia, Pediatric Critical Care, Philadelphia, Pennsylvania. *Correspondence to: Jambunathan Krishnan, M.D., Rm. 2201, Divn. of Pediatric Critical Care, Cardinal Glennon Childrens Medical Center, 1465 S. Grand Blvd., St. Louis, MO 63104. E-mail: jkrishna@slu.edu. Received 13 June 2006; Accepted 11 August 2006. DOI 10.1002/ppul.20550 Published online in Wiley InterScience (www.interscience.wiley.com).

84 Krishnan and Morrison APRV with initial settings P High 37 cm H 2 OP Low 0cm H 2 OT High 2.5s T Low 0.5 sec. OI decreased from 24 (P aw 24 cm H 2 O, PaO 2 60 mm Hg) on conventional MV to 9.8 (P aw 29 cm H 2 O, PaO 2 118 mm Hg) over the next 3.5 days, on eventual APRV settings of P High 32 cm H 2 O P Low 0cmH 2 OT High 3 sec T Low 0.6 sec, FiO 2 0.4. No NMB was required. He was weaning on APRV when a new episode of gram negative sepsis led to his death. Case 3 A 5-year-old male with a history of 60% body surface area burns and sepsis developed ARDS. On PC with PIP/PEEP 39/19 and FiO 2 0.9 his OI was 36.4 (P aw 32 cm H 2 O, PaO 2 79 mm Hg). On HFOV he developed intractable hypercarbia with a pco 2 of 121 mm Hg. On APRV with P High 40 cm H 2 OP Low 0cmH 2 OT High 4 sec T Low 0.8 sec his OI remained elevated but his pco 2 improved to 78 mm Hg. At one point he had a mean airway pressure (P aw )of41cmh 2 O with P High 43 cm H 2 OP Low 3 cm H 2 OT High 5.5 sec T Low 0.6 sec. His multiorgan failure worsened, he had an order placed limiting resuscitation attempts, and he died several days later. Case 4 An 8-year-old male with cystic fibrosis and deteriorating pulmonary status developed ARDS following a bronchoscopy. Severe agitation resulting in large sedative doses led to difficulty weaning off MV. APRV was begun 4 days after the procedure. Prior to the change he was on FiO 2 of 0.5 with PIP/PEEP of 30/13 and an OI of 12.7. On APRV (initially P High 28 cm H 2 OP Low 0cmH 2 OT High 3.5 sec T Low 0.5 sec) his sedation requirements decreased and he was extubated to noninvasive positive pressure ventilation 3 days later. No NMB was needed on conventional MV or APRV. Case 5 Fig. 1. Pressure-time curve on APRV. A 4-year-old male presented with persistent fever, jaundice, hepatomegaly, pancytopenia, and hypofibrinogenemia. He progressed to shock, respiratory failure, ARDS, and multiorgan failure. Continuous hemofiltration was begun. His OI on PRVC (TV 250 PEEP 10 cm H 2 O FiO 2 1.0 with PIPs over 40 cm H 2 O) was 23.4 (P aw 18 cm H 2 O, PaO 2 77 mm Hg). He was transitioned to APRV with initial settings P High 34 cm H 2 OP Low 0cmH 2 OT High 3 sec T Low 0.4 sec. T High was lengthened to 4.5 sec and his FiO 2 was then weaned to 0.6. NMB was lifted. His oxygenation status improved with the OI decreasing to 13.1 (P aw 31 cm H 2 O, PaO 2 142 mm Hg) over the next 3 days on settings of P High 34 cm H 2 OP Low 0cmH 2 OT High 4 sec T Low 0.4 sec FiO 2 0.6. He had been weaned to CPAP and his shock had resolved when he suffered an intracranial hemorrhage which led to his death. Autopsy revealed hemophagocytic lymphohistiocytosis. Case 6 A 16-year-old healthy female collapsed playing field hockey. Bystander cardiopulmonary resuscitation was begun and paramedics defibrillated her successfully for ventricular fibrillation. She was found to have hypertrophic cardiomyopathy, ventricular septal infarction, and aspiration pneumonia. She required hand bagging with extremely high pressures to keep her oxygen saturation >80% and so was placed on HFOV with P aw 37 cm H 2 O, Amplitude of 60, a frequency of 4 Hz, T i 33% and FiO 2 1.0. Over the next 12 hr she was weaned to P aw 28 cm H 2 O and FiO 2 0.6. A decision was made to take her to cardiac catheterization and it was felt that the procedure would be easier off of HFOV, so she was changed to APRV with settings P High 25 cm H 2 OP Low 0cmH 2 OT High 4.5 sec T Low 0.5 sec. She remained on APRVafter her return to the ICU and weaned over a few days until she was transitioned to SIMV PRVC. A few days later she was again placed on APRV, initially at P High 34 cm H 2 OP Low 0cmH 2 OT High 4.5 sec T Low 0.6 sec after a severe episode of derecruitment with suctioning. She weaned well off the ventilator, had an automatic implantable cardioverter/defibrillator placed and was discharged home doing well on betablockade. Case 7 A 1-year-old male with a history of leukemia, bone marrow transplant and tracheostomy was admitted for sepsis, neutropenia and graft versus host disease. He developed ARDS with an OI of 14.6 (P aw 18 cm H 2 O, PaO 2 123 mm Hg) on PRVC (TV 160 P aw 18 cm H 2 O FiO 2 1.0) and had difficulty ventilating (pco 2 ¼ 64 mm Hg with tachypnea and distress), thought to be due to a large leak around the tracheostomy. He was more comfortable on APRV (initially P High 30 cm H 2 OP Low 0cmH 2 OT High 3 sec T Low 0.4 sec and rapidly weaned in 72 hr to a P High 19 cm H 2 OP Low 0cmH 2 OT High 5.5 sec T Low 0.6 sec); his

APRV: Pediatric Case Series 85 OI was 6.6 (P aw 17 cm H 2 O, PaO 2 115 mm Hg) on FiO 2 0.45 and pco 2 was 39 mm Hg. Relapsed leukemia was confirmed, he developed renal failure, his family decided against dialysis, and he died several days later. DISCUSSION In contrast to conventional MV, APRV cycles between high and low set pressures with the vast majority of time in the respiratory cycle spent at the high pressure. Unlike inverse ratio ventilation, the patient can breathe spontaneously throughout the entire cycle. Alveolar collapse is typically prevented by keeping the time at the lower pressure very brief rather than by providing high positive end expiratory pressure. 6 The higher CPAP level is known as P High or P1 and the lower pressure level as P Low or P2. The time spent at high and low pressure is known as T High (T1) and T Low (T2) respectively (Fig. 1). The APRV mode it is also known as Bi Level or Bi-Vent on the Puritan Bennett and the Servo-i ventilators, respectively. When initiating APRV for hypoxemic respiratory failure, one method is to set the P High at approximately the plateau pressure on conventional MV. Plateau pressure is the best clinical estimate of the average alveolar pressure. 7 The P High should then be increased as necessary in order to allow the FiO 2 to be weaned to a less toxic level (a cutoff of 0.6 is often used). Our practice has been to keep the P Low at zero, as described by Frawley and Habashi, 6 which facilitates maximum acceleration of expiratory gas flow and minimizes the time required for release ventilation. We usually begin with a T High of 3.5 5.5 sec. The long T High maintains the P aw and hence alveolar recruitment. The appropriate T Low depends on Fig. 2. Flow-time curve on APRV showing optimal expiratory flow pattern.

86 Krishnan and Morrison the expiratory time constants of the lungs (Time constant ¼ compliance resistance). An optimal release time allows for adequate ventilation while minimizing lung volume loss. A short release time should impede complete exhalation in the slower compartments (i.e., areas of high compliance or resistance to exhalation) and generate regional intrinsic PEEP. Theoretically this will enhance alveolar recruitment. 8,9 Our practice is to adjust the T Low until the patient s expiratory flow during the release phase (Fig. 2) reaches approximately 50 75% of its peak value. 6 The time constant may vary with any change in the lung function, and a longer release phase may become appropriate as lung disease improves. Any change in the patient s condition or ventilator settings requires reevaluation of the expiratory gas flow pattern. The T Low in children may need to be shorter than that usually used in adults, 4 and in our series ranged from 0.4 to 0.8. As we gained experience, we usually started T Low at 0.4 0.5 sec. Oxygenation improved in several of our patients managed with APRV (Fig. 3), although this could have been due to improvement with time rather than the change in mode of ventilation. We report oxygenation using the OI which is calculated as: OI ¼ (mean airway pressure FiO 2 100)/P a O 2. This index is the most commonly used marker of the severity of hypoxemic respiratory failure in pediatrics as it includes both the pressure used and oxygen administered to achieve a certain degree of oxygenation. A higher number reflects worse lung disease. In addition to raising the P high, Fig. 3. Change in OI in each case over time. Data points are approximately 12 hr apart. The OI for the patient in case 6 is for her second period on APRV. Case 3 is not included in the graph as pre- APRV data was not available.

APRV: Pediatric Case Series 87 lengthening the T high can increase the P aw and improve oxygenation. On APRV the P aw is calculated as: ½ðP High T High ÞþðP Low T Low ÞŠ ðt High þ T Low Þ In general, the P aw was higher and peak airway pressures lower when our patients were changed to APRV, allowing the FiO 2 to be weaned. In our experience, alveolar ventilation was adequate on APRV. PaCO 2 levels improved over prior modes in three patients (Cases 1, 3, and 7). Ventilation in APRV occurs during the release phase and during spontaneous breathing at any point in the cycle. In a patient who is not breathing spontaneously, the T High may need to be shortened to allow more frequent releases and increase minute ventilation. Increasing the pressure differential between P High and P Low by increasing P High can also decrease PaCO 2 by augmenting the release volume. In adults, APRVachieves equally effective alveolar ventilation with lower minute ventilation compared to conventional positive pressure ventilation, suggesting less dead space ventilation. 10 One method of weaning on APRV is the drop and stretch technique. 6 The T High is lengthened and the P High is lowered in a stepwise fashion, thus allowing a slow, controlled wean of P aw, until a low enough level of CPAP (no release phase) is reached from which the patient can be extubated. Lengthening the T High in this fashion is usually only tolerated when the patient is breathing spontaneously. The literature in adults suggests that less sedation is required and NMB generally avoided on APRV. 11 13 None of our patients required NMB; however, there did not seem to be a general decrease in sedative requirements. Minimizing NMB both avoids toxicity of these agents and allows spontaneous breathing. Maintaining spontaneous breathing is beneficial when using APRV, particularly when compared to other rescue modes such as high frequency ventilation, and in fact it can be challenging to apply APRV in patients who have no respiratory effort. Spontaneous breathing with APRV improves alveolar ventilation and has been shown to improve V/Q matching in both adult 14 and animal studies. 15 It improves renal blood flow 16 and intestinal perfusion. 17 Spontaneous breathing in conjunction with APRV decreases respiratory work and normalizes respiratory muscle blood flow in acute lung injury. 18 None of our patients deteriorated hemodynamically when they were changed to APRV. In adults, APRV has been shown to improve cardiac performance with ARDS 19 and has been used in postoperative pediatric cardiac surgery patients with no cardiocirculatory adverse effects noted. 20 Larger studies will be needed to determine if adverse hemodynamic effects are a concern in children. The theory behind APRV and HFOV is similar: maintaining a higher P aw without high peak pressures as a lung protective strategy. Potential advantages of APRV over HFOV include the ease of spontaneous breathing, lower NMB requirements, possibly lower sedative requirements, less noise, and no need to maintain a separate set of ventilators. Our staff found patient care and procedures more straightforward on APRV, as in Case 6. Although pediatric centers are beginning to experiment with APRV, there is no comparative data available with other modes of ventilation. If its theoretical benefits lead to its increasing application in pediatrics, direct comparisons with modes of ventilation such as HFOV, with which there is a much longer pediatric experience, are essential. Our center s experience was that the physician, nursing and respiratory staff rapidly became comfortable with APRV; as we gain experience with it we are beginning to transition patients before their lung disease becomes too severe, which we hope will lead to improvements in the relatively high mortality seen in this case series where APRV was used predominantly as a rescue mode after all other modes had failed. Whether earlier use makes a difference remains to be seen. We have also found that the flow dynamics make it a useful mode in patients with a large leak around an endotracheal tube or tracheostomy (e.g., Case 7), even when they do not have severe hypoxemia. CONCLUSION APRV is a new mode of ventilation which is beginning to be applied in pediatrics. In theory, it is consistent with a lung protective approach while having some hypothetical advantages over HFOV; however, comparative studies need to be done. 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