**7. Special populations potentially with pulmonary hypertension**

#### **7.1. Pediatrics**

Pediatric patients with PH have some unique clinical features comparing with adult PH patients. Genetic factors seem to play a more important role in the pathogenesis of PH. Chida *et al* studied fifty-four patients with IPAH or HPAH whose disease was diagnosed at <16 years of age. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers. Overall 5-year survival for all patients was 76%. Eighteen BMPR2 mutation carriers and 7 ALK1 mutation carriers were detected in the 54 patients with childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers than mutation noncarriers (55% vs 90%, hazard ratio 12.54, p = 0.0003). ALK1 mutation carriers also had a tendency to have worse outcome than mutation noncarriers (5-year survival rate 64%, hazard ratio 5.14, p=0.1205). These indicated that patients with childhood IPAH or HPAH with BMPR2 mutation have the poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes than mutation non-carriers. It is important to consider aggressive treatment for BMPR2 or ALK1 mutation carriers [102]. Carmosino *et al* retrospectively studied 156 children with PH with median age 4.0 years who underwent anesthesia or sedation for noncardiac surgical procedures or cardiac catheteriza‐ tions from 1999 to 2004. PH etiology was 56% idiopathic (primary), 21% AHD, 14% chronic lung disease, 4% chronic airway obstruction, and 4% chronic liver disease. Baseline PAP was subsystemic in 68% patients, systemic in 19%, and suprasystemic in 13%. The anesthetic techniques were 22% sedation, 58% general inhaled, 20% general IV. Minor complications occurred in eight patients (5.1% of patients, 3.1% of procedures). Major complications includ‐ ing cardiac arrest and pulmonary hypertensive crisis, occurred in seven patients during cardiac catheterization procedures (4.5% of patients, 5.0% of cardiac catheterization procedures, 2.7% of all procedures). There were two deaths associated with pulmonary hypertensive crisis (1.3% of patients, 0.8% of procedures). Based on their observation, they believe baseline suprasys‐ temic PH was a significant predictor of major complications by multivariate logistic regression analysis (OR = 8.1, P = 0.02) and complications were not significantly associated with age, etiology of PH, type of anesthetic, or airway management. Children with suprasystemic PH have a significant risk of major perioperative complications, including cardiac arrest and pulmonary hypertensive crisis [103]. Management of pediatric patients with PH poses unique challenges to pediatric anesthesiologists: PAC may not be available for many smaller pediatric patients due to the small sizes of their cardiac chamber and blood vessels. TEE may not be available to some pediatric patients due to lack of suitable size of TEE probe. So transthoracic or epicardial echocardiography will play a much more important role for those pediatric patients without TEE and PAC. Minimally invasive/non-invasive monitoring of MAP, CO/CI, SVV may play some role intraoperatively, however these current technologies may not work as well in children as in adults [104]. And information from randomized controlled clinical studies on the treatment of pediatric PH is currently very limited, unanimous opinions are to refer to the guidelines and treatment strategies for the treatment of adult PH. Therefore, the recommended treatment for children is only grade IIa with the level of evidence class C.

#### **7.2. Obstetrics**

patient can develop sudden worsening of PH and RV ischemia. Thus weaning from the ventilatory support and endotracheal extubation should be done gradually with close attention to adequate oxygenation, ventilation and analgesia. Even routine events such as bucking on the ventilator due to tracheal stimulation, while tolerated by the average patient, can lead to acute rises in PVR and RV failure in patient with severe PH [78]. Postoperative pain manage‐ ment of patients with PH warrants special attention, because in clinical practice, the most commonly used analgesic agents are opioids which are potent respiratory depressants also. Depression of respiratory drive will likely cause hypoventilation which leads to increased PAP. Thus using multimodal analgesic strategy is critical in minimizing the side effect of respiratory inhibition by opioids and avoiding hypoventilation-associated increase of PAP.

**7. Special populations potentially with pulmonary hypertension**

Pediatric patients with PH have some unique clinical features comparing with adult PH patients. Genetic factors seem to play a more important role in the pathogenesis of PH. Chida *et al* studied fifty-four patients with IPAH or HPAH whose disease was diagnosed at <16 years of age. Functional characteristics, hemodynamic parameters, and clinical outcomes were compared in BMPR2 and ALK1 mutation carriers and noncarriers. Overall 5-year survival for all patients was 76%. Eighteen BMPR2 mutation carriers and 7 ALK1 mutation carriers were detected in the 54 patients with childhood IPAH or HPAH. Five-year survival was lower in BMPR2 mutation carriers than mutation noncarriers (55% vs 90%, hazard ratio 12.54, p = 0.0003). ALK1 mutation carriers also had a tendency to have worse outcome than mutation noncarriers (5-year survival rate 64%, hazard ratio 5.14, p=0.1205). These indicated that patients with childhood IPAH or HPAH with BMPR2 mutation have the poorest clinical outcomes. ALK1 mutation carriers tended to have worse outcomes than mutation non-carriers. It is important to consider aggressive treatment for BMPR2 or ALK1 mutation carriers [102]. Carmosino *et al* retrospectively studied 156 children with PH with median age 4.0 years who underwent anesthesia or sedation for noncardiac surgical procedures or cardiac catheteriza‐ tions from 1999 to 2004. PH etiology was 56% idiopathic (primary), 21% AHD, 14% chronic lung disease, 4% chronic airway obstruction, and 4% chronic liver disease. Baseline PAP was subsystemic in 68% patients, systemic in 19%, and suprasystemic in 13%. The anesthetic techniques were 22% sedation, 58% general inhaled, 20% general IV. Minor complications occurred in eight patients (5.1% of patients, 3.1% of procedures). Major complications includ‐ ing cardiac arrest and pulmonary hypertensive crisis, occurred in seven patients during cardiac catheterization procedures (4.5% of patients, 5.0% of cardiac catheterization procedures, 2.7% of all procedures). There were two deaths associated with pulmonary hypertensive crisis (1.3% of patients, 0.8% of procedures). Based on their observation, they believe baseline suprasys‐ temic PH was a significant predictor of major complications by multivariate logistic regression analysis (OR = 8.1, P = 0.02) and complications were not significantly associated with age, etiology of PH, type of anesthetic, or airway management. Children with suprasystemic PH have a significant risk of major perioperative complications, including cardiac arrest and

**7.1. Pediatrics**

222 Pulmonary Hypertension

Curry *et al* reported two maternal deaths out of 12 pregnancies in 9 patients. One of the two deaths was related to pre-eclampsia and the other related to cardiac arrhythmia. Maternal morbidity included postpartum hemorrhage (five cases), and one post-caesarean evacuation of a wound hematoma. There were no perinatal death, nine live births and three first-trimester miscarriages. Mean birthweight was 2197 grams, mean gestational age was 34 weeks (range 26-39), and mean birthweight percentile was 36 (range 5-60). Five babies required admission to the neonatal intensive care unit, but were all eventually discharged home. All women were delivered by caesarean section (seven elective and two emergency deliveries), under general anesthesia except for one emergency and one elective caesarean performed under regional block [105]. Maternal and fetal outcomes for women with PH has improved; however, the risk of maternal mortality remains significant, so that early and effective counseling about contraceptive options and pregnancy risks should continue to play a major role in the man‐ agement of such women when they reach reproductive maturity.

#### **8. Summary**

We have gained better understanding of PH and have significantly more sophisticated management strategies now compared with two decades ago. PH can develop due to pulmo‐ nary vascular remodeling (cellular proliferation), abnormal vasoconstriction, mechanical obstruction (chronic thromboembolic events, interstitial lung diseases) or left-side heart diseases. Thorough preoperative evaluation is mandatory. A clear understanding of the etiology of pulmonary hypertension is extremely important to understand how to optimally manage these patients in the operating room. Echocardiography plays a key role in preliminary screening, monitoring the progress and evolution of PH, and intraoperative monitoring and treatment. Right heart catheterization remains the gold standard for the diagnosis of PH. Evaluation of the overall pulmonary functional status is also important in assessing patients' tolerability to the planned surgical procedure. Perioperatively these patients can present very challenging clinical scenarios due to the complexity of their PH and increased risks for significant complications with elevated morbidity and mortality. Several clinical characteris‐ tics predict early mortality: right axis deviation, right ventricular hypertrophy, RVSP/SBP ratio above 0.6, and intraoperative use of epinephrine or dopamine. Intraoperative control of elevated pulmonary pressure can be achieved with inhaled nitric oxide or prostacyclin, PDE inhibitors (milrinone, sildenafil), calcium channel blockers, nitrodilators and adequate oxygenation. The ideal perioperative care of these patients requires a multidisciplinary approach with appropriate planning for pre-procedural optimization, comprehensive intraoperative monitoring and delicate management of PAP as well as intensive care unit monitoring in the postoperative period. This approach will test the expertise and resources of medical institutions. Anesthesiologists will require a thorough understanding of the current treatment options, pathophysiology of the disease, and the implications of various anesthetic agents and techniques to provide the highest level of patient safety and care to the patients with PH.

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