PH is a frequently encountered pathophysiological disorder in ICU and is… (Location 17175)
The classification splits PH into five diagnostic groups according to underlying cause and therefore likely to have… (Location 17178)
important distinction to note is that group 1 PH or pulmonary arterial hypertension (PAH), previously known as primary PH, includes a set of disorders where PH is the primary problem. In contrast, all other classification groups are due to conditions that lead to PH as a result of cardiac dysfunction, abnormalities in the lung… (Location 17179)
Box 24.5 Clinical classification of pulmonary hypertension 1. Pulmonary arterial hypertension (PAH) 1.1 Idiopathic 1.2 Familial 1.2.1 BMPR2 1.2.2 ALK1, endoglin (with or without hereditary haemorrhagic telangiectasia) 1.2.3 Unknown 1.3 Drug and toxin induced 1.4 Associated with: 1.4.1 Connective tissue diseases 1.4.2 HIV infection 1.4.3 Portal hypertension 1.4.4 Congenital heart diseases 1.4.5 Schistosomiasis 1.4.6 Chronic haemolytic anaemia 1.5 Persistent pulmonary hypertension of the newborn 1′. Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis 2. Pulmonary hypertension due… (Location 17183)
3.1 Chronic obstructive pulmonary disease 3.2 Interstitial lung disease 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4 Sleep-disordered breathing 3.5 Alveolar hypoventilation disorders 3.6 Chronic exposure to high altitude 3.7 Developmental abnormalities 4. Chronic thromboembolic pulmonary hypertension 5. Pulmonary hypertension with unclear and/or multifactorial mechanisms 5.1 Haematological disorders: myeloproliferative disorders, splenectomy 5.2 Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis 5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 5.4 Others: tumoural obstruction, fibrosing mediastinitis, chronic renal failure on dialysis ALK1, Activin receptor-like kinase 1 gene; BMPR2, bone morphogenetic protein receptor type 2; HIV, human immunodeficiency virus; PAH, pulmonary arterial hypertension.… (Location 17196)
PH is defined as a mean pulmonary arterial pressure (mPAP) greater than or equal to 25 mm Hg on right heart… (Location 17211)
common pathological conditions leading to PH include severe respiratory failure,147 acute respiratory distress syndrome (ARDS),148 left-sided heart failure leading to increased LAP,149 massive PE,150 mechanical… (Location 17213)
PH in many of these conditions is associated with… (Location 17218)
several factors including sepsis, cardiac arrhythmias, and treatment failure can precipitate acute exacerbations of chronic PAH leading to ICU admissions. Sepsis in… (Location 17221)
Several disorders lead to PH in ICU, yet there are no consensus or international guidelines that exist to assist with… (Location 17223)
success. Invariably the most crucial manifestation of PH is RV dysfunction. (Location 17231)
Under normal conditions RV outflow is to a high-compliance, low-pressure… (Location 17232)
thin-walled RV is highly sensitive to small increases in the PVR leading to ventricular dilation, an increase in end-systolic volume, and reduced RV… (Location 17233)
In the initial stages the RV responds by enhancing contractility in… (Location 17234)
Further increases in RV afterload overwhelm these compensatory mechanisms resulting in reduced CO and… (Location 17235)
In the setting of increased afterload the dilated RV loses its normal shape and pushes the septum towards the LV, thereby… (Location 17238)
RV dilation can also lead to tricuspid regurgitation… (Location 17240)
a fall in systemic blood pressure can compromise RV coronary perfusion, thereby leading to ischaemia… (Location 17241)
under normal conditions coronary perfusion to the RV is maintained… (Location 17242)
RV pressure increases there is a decrease in the perfusion pressure gradient between the aorta and the RV during systole, thereby limiting… (Location 17243)
Acute Cor Pulmonale Acute cor pulmonale (ACP) is caused by acute pressure overload of the RV due to an acute increase in PVR and thus RV afterload. The RV dilates acutely, RV systolic function is impaired and the interventricular… (Location 17245)
commonly seen in critically ill patients with severe ARDS and… (Location 17249)
was historically reported to be 50%–60%; however this has reduced to 20%–30% following the widespread adoption of lung… (Location 17250)
ACP is independently associated with increased mortality in patients with severe ARDS and will ultimately result in acute circulatory… (Location 17252)
management of patients with PH is diagnosis of the underlying cause and, if feasible, treatment should focus on prompt… (Location 17254)
provides information on RV and LV structure and function, pericardial effusions and… (Location 17267)
a recent systematic review found only modest correlation between pulmonary pressures determined by echocardiography and those… (Location 17268)
adequate oxygenation applies to most critically ill patients but assumes… (Location 17272)
RV myocardial oxygen demands are increased in severe PH and hypoxia may increase PVR by precipitating hypoxic… (Location 17273)
mechanical ventilation may be unavoidable; however, it comes at a cost. Positive-pressure ventilation has adverse effects on RV afterload and along with… (Location 17274)
Ventilatory strategies should focus on maintaining adequate oxygenation whilst avoiding… (Location 17275)
The RV predominantly relies on adequate filling to maintain CO. Conversely, RV dilation as a consequence of volume overload can lead to impaired RV function and impaired LV filling, due to ventricular… (Location 17277)
In patients with evidence of RV volume overload and septal bowing, aggressive fluid removal, with diuretics54 or renal replacement therapy, should be considered as it may… (Location 17279)
The maintenance of sinus rhythm in these patients will improve RV… (Location 17281)
Vasopressors and inotropes The goal of using vasoactive drugs in patients with RV dysfunction secondary to PH is to maintain an adequate CO whilst avoiding increases in PVR and cardiac arrhythmias. In the face of systemic hypotension norepinephrine, a powerful… (Location 17284)
Improving systemic blood pressure has the additional benefit of improving coronary perfusion. However, norepinephrine also… (Location 17287)
animal model of acute PH, administration of norepinephrine restored systemic blood pressure and increased PAP.169 Overall, the effect was to improve both RV contractility and CO. In the same study, animals treated with dobutamine showed a greater… (Location 17288)
In clinical studies, dobutamine has been shown to improve RV performance in ischaemic failure.170 Evidence from these studies suggest that low-dose dobutamine may be… (Location 17291)
Increases in myocardial oxygen demand and tachyarrhythmias may preclude dobutamine use in all patients with PH. Vasopressin can also be considered as an alternative to norepinephrine; in addition to powerful systemic vasoconstriction, it… (Location 17293)
use of levosimendan and dobutamine in PH was compared. Improvement in RV contractility was similar after administration of both… (Location 17296)
similar trend of improved RV contractility and reduced PVR following the administration of… (Location 17298)
levosimendan appears to be a promising alternative to dobutamine with the additional benefit of PVR reduction without… (Location 17300)
PDE-3 inhibitors, such as milrinone, have inotropic and vasodilating properties. They can improve CO by reducing PVR and increasing RV contractility. PDE-3 inhibitors have been shown to successfully reduce… (Location 17301)
milrinone may require additional vasopressor support, given its propensity for… (Location 17306)
Inhaled nitric oxide (iNO) increases production of cyclic guanosine monophosphate (cGMP) and is a potent pulmonary vasodilator. It results in the reversal of hypoxic pulmonary vasoconstriction, reduction in PVR and improved oxygenation. (Location 17315)
iNO therapy has been shown to reduce PVR and improve RV stroke work in postoperative cardiothoracic patients with PH. (Location 17317)
severe ARDS and hypoxia refractory to maximal medical treatment, iNO commonly provides 48 hours improvement in oxygenation, but fails to reduce the length of mechanical ventilation or improve mortality. (Location 17319)
Methaemoglobinaemia and nitrogen dioxide (NO2) production are recognised adverse effects, and rebound PH may also occur after abrupt cessation of iNO. (Location 17322)
Inhaled and intravenous prostacyclins are also used as vasodilators in PH. Inhaled prostacyclin (epoprostenol) use is associated with significant reduction in mPAP and improvement in ICU patients with PH. (Location 17324)
Inhaled iloprost, a synthetic prostacyclin analogue, has been shown to reduce mPAP and improve RV function in PH post-cardiopulmonary bypass. (Location 17326)
Phosphodiesterase-5 (PDE-5) inhibitors stop the degradation of cGMP leading to vasodilation. In patients with chronic PAH, oral sildenafil, a selective PDE-5 inhibitor, has been shown to reduce mPAP189 and improve CO by reducing PVR. (Location 17330)
Sildenafil has also been used as a bridge to avoid rebound hypotension following iNO withdrawal in post-cardiac-surgery patients. (Location 17333)
Mechanical devices In patients where all other treatment options have been exhausted, lung transplantation may be the only viable option. (Location 17336)
Extracorporeal life support has also been described as a bridge to transplantation. (Location 17338)
VA-ECMO will help to unload the RV, reduce RV afterload and improve perfusion of vital organs and thus may provide temporary support in the acute situation. (Location 17338)
Summary PH and consequent RV dysfunction are frequently encountered in the ICU with a high associated mortality (Location 17342)
Prompt identification of the underlying cause and its treatment should be the main focus of management. There is very little evidence for the use of specific treatments in the ICU setting (Location 17343)
A few general principles, such as optimising fluid status, optimising HR and rhythm, avoiding high-pressure ventilation, maintaining coronary perfusion by optimising systemic pressure, inotropic support for RV dysfunction and inhaled pulmonary vasodilation may be applied where appropriate. (Location 17345)
of individual therapies should be guided by an understanding of their mechanism of action and the expected physiological response in an individual patient. The response should be monitored closely to avoid adverse events and to optimise therapy. (Location 17347)