She was known to have normal left ventricular function but moderate to severely impaired right ventricular function. At presentation she had sepsis and was hypotensive.
The patient was optimized for theatre with i. Anaesthesia was induced, with invasive monitoring in situ. A cardiostable modified rapid sequence induction was performed.
Maintenance of anaesthesia was with sevoflurane. Once hypovolaemia had been corrected, systemic hypotension was treated with norepinephrine, and early introduction of vasopressin. The patient was transferred to intensive care after surgery. A transthoracic echocardiogram was performed on intensive care.
This showed right heart failure, and milrinone was added. The patient's acid—base status began to improve. The next morning a sedation hold was performed followed by successful extubation. Fundamental Principles and Practice of Anaesthesia. Control of the pulmonary circulation. Anaesthesia and the Lung.
Dordrecht: Kluwer , ; 9 — Google Scholar. Google Preview. Lumb AB , Slinger P. Hypoxic pulmonary vasoconstriction.
Physiology and anaesthetic implications. Anesthesiology ; : — Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans. Chest ; : — Physiol Rev ; 92 : — Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA ; : — Influence of age on atelectasis formation and gas exchange impairment during general anaesthesia. Br J Anaesth ; 66 : — Effects of sevoflurane on hypoxic pulmonary vasoconstriction in anaesthetized piglets.
Br J Anaesth ; 85 : — 5. Desflurane and isoflurane produce similar alterations in systemic and pulmonary hemodynamics and arterial oxygenation in patients undergoing one-lung ventilation during thoracotomy.
Anesth Analg ; 87 : — 7. Pulmonary vascular responses to nitrous oxide in patients with normal and high pulmonary vascular resistance. Anesthesiology ; 57 : 9 — Propofol does not inhibit hypoxic pulmonary vasoconstriction in humans. J Clin Anesth ; 1 : — 8. Ng A , Swanevelder J. Hypoxaemia during one-lung anaesthesia. Eur Respir J ; 34 : — Mykola VT , Arseniy V et al. Arterial pulmonary hypertension in noncardiac intensive care unit.
Vasc Health Risk Manag ; 4 : — Mechanisms and drug therapy of pulmonary hypertension at high altitude. High Alt Med Biol ; 14 : — Nebulized milrinone use in a pulmonary hypertensive crisis. Pharmacotherapy ; 27 : — 6. Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis. Br Med J ; : Pulm Pharmacol ; 3 : 59 — Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure.
Crit Care Med ; 32 : — Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review. Critical Care ; 14 : R Oxford University Press is a department of the University of Oxford.
It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Physiology. Clinical implications of HPV. Drug effects on HPV.
Clinical case report. In both cells, hypoxia has been shown to inhibit an outward potassium current, thus causing membrane depolarization and calcium entry through the voltage-dependent calcium channels. In both cells there is evidence to suggest that changes in the redox status of the oxygen-sensitive potassium channel or channels may control current flow, so that the channel is open when oxidized and closed when reduced.
More studies are needed to precisely define the individual potassium channels responsive to hypoxia and to confirm the gating mechanism. In systemic arteries hypoxia causes an increased current through ATP-dependent potassium channels and vasodilatation, whereas in the pulmonary arteries hypoxia inhibits potassium current and causes vasoconstriction.
Abstract Hypoxia causes constriction in small pulmonary arteries and dilatation in systemic arteries. Cellular energy state. Even when hypoxic, cellular levels of high-energy molecules such as adenosine triphosphate and phosphocreatine are well maintained by glycolysis, provided glucose remains freely available.
Adenylate kinase activity converts any available adenosine diphosphate molecules into adenosine triphosphate, increasing adenosine monophosphate levels. Membrane-bound protein function. Hemeoxygenase is a membrane-bound enzyme, normally responsible for heme degradation, which is also sensitive to P o 2. A normal product of hemeoxygenase activity is carbon monoxide, which suppresses pulmonary vascular reactivity, so although not directly an oxygen sensor in HPV hemeoxygenase does influence the response.
Hypoxia-inducible factor HIF is a ubiquitous cellular enzyme responsible for initiating transcription of many hypoxia-induced genes. The activity of prolyl hydroxylase domains is dependent on oxygen across a wide range of P o 2 levels, and the action of HIF itself on DNA is also oxygen dependent, so both its stabilization and activity are oxygen sensitive.
Prolyl hydroxylase domain activity is also dependent on iron concentration within the cytoplasm, potentially explaining the dependence of HPV on iron status. Cyclooxygenase and lipoxygenase use molecular oxygen as a substrate so are inherently oxygen sensitive. Activity of both leads to the generation of many vasoactive prostanoids and leukotrienes, so alteration of their activity by hypoxia can have variable effects on the pulmonary vasculature.
Evidence suggests that cyclooxygenase and lipoxygenase activity are not primarily responsible for oxygen sensing in HPV but may be involved in modulating the response. With so many contenders for the role of HPV oxygen sensor, it is unsurprising that no consensus exists on how this happens in vivo. Many of the mechanisms described are interlinked, and multiple mechanisms almost certainly involved depending on the phase of HPV, degree of hypoxia, etc.
Both mechanisms are believed to occur in HPV. The situation is, however, more complex, with the sensitivity of the PASMC myofilament to calcium being variable. Intrinsic factors such as phosphorylation by protein kinase C or external factors such as nitric oxide release or stimulation by endothelin may all contribute to increased calcium sensitivity during hypoxia. Modulation describes systems that enhance or inhibit HPV but are not required for the response to occur.
Numerous mediators are released by ECs in response to hypoxia:. Nitric oxide is produced by both constitutive endothelial and inducible nitric oxide synthase NOS. Basal nitric oxide production by endothelial NOS is believed to maintain the pulmonary circulation in a permanent state of active vasodilation.
NOS uses molecular oxygen and l -arginine to synthesize nitric oxide, so in hypoxic conditions, the synthesis of nitric oxide is reduced.
However, reversal of basal nitric oxide production would only account for a small proportion of the total HPV response seen and expired nitric oxide, a marker of basal nitric oxide production, is not significantly associated with the onset of HPV on ascent to altitude.
Prostacyclin PGI 2 is a vasodilator released by both pulmonary and systemic ECs acting via stimulation of adenylate cyclase and increased cyclic adenosine monophosphate production. Endothelin-1 is a small peptide 21 amino acids , which is a potent pulmonary vasoconstrictor. Stimulation of the pulmonary vasculature by endothelin produces an intense and prolonged vasoconstriction.
Endothelin has also been implicated in the vascular remodeling that occurs in the pulmonary vasculature with long-term hypoxia. As a result, endothelin antagonist drugs see Endothelin Antagonists are important in the treatment of chronic pulmonary hypertension.
Animal studies have demonstrated many humoral modulators of HPV such as adenosine, histamine, and 5-hydroxytryptamine, none of which are believed to play a significant role in humans. These nerves may be involved in the development of some types of pulmonary edema, including neurogenic pulmonary edema and HAPE. Parasympathetic and sensory nerves in the lung are not believed to modulate HPV.
As soon as the pulmonary circulation develops in the fetus, HPV is believed to be present and active. The high PVR results from:. The presence of fluid in the alveoli. In late pregnancy, fetal breathing movements cause fluid to be sucked into the lung and maintain this at a slightly positive pressure. This is believed to not only prevent lung collapse and stimulate cell growth in the developing lung but also compresses the pulmonary vasculature.
A variety of vasodilator and vasoconstrictor systems exist in the fetal pulmonary circulation, but the balance of these strongly favors vasoconstriction. The mechanisms of HPV in utero differ from those in adults. In the late stages of pregnancy, fetal physiology changes in preparation for birth, in particular, endothelin production declines.
At birth, PVR must reduce quickly and permanently, which results from a combination of the following effects:. Lung expansion. Compression of the chest during parturition is followed by sudden expansion and increased lung volume at birth. Increased P o 2 in the lung at birth decreases PVR by reversing HPV, particularly that resulting from endothelin stimulation, and probably also by increasing nitric oxide production by ECs.
Increased systemic vascular resistance from loss of the placental circulation and closure of the ductus arteriosus raises left-sided pressures in the heart leading to foramen ovale closure. Pulmonary blood flow therefore increases, and recruitment and distension of pulmonary capillaries facilitate this.
This distension of blood vessels may contribute to further pulmonary vasodilatation by causing ECs to release vasodilator modulators in response to increased shear stress on the cells. Mechanical deformation of the lungs may be responsible for the release of vasodilator modulators by pulmonary ECs and so reduced intensity of HPV.
Possible mechanisms include increased production of prostacyclin and nitric oxide and increased BK Ca sensitivity. After the dramatic pulmonary vasodilation at birth, PVR continues to decrease further in the first few days and weeks of neonatal life.
However, until this occurs, HPV is a dangerous reflex as the highly muscular pulmonary vessels can effectively shut down the pulmonary circulation and return the neonate to a fetal circulation and dangerously low arterial P o 2.
In adults, matching of alveolar ventilation and perfusion is crucial to optimize gas exchange, particularly oxygenation. In the extreme example of all ventilation going to one lung and perfusion to the other, overall ratio will still be 1, but no gas exchange will occur. HPV therefore serves to reduce blood flow through areas of lung where P o 2 is low, as illustrated in figure 4. Blood flowing through all regions is fully saturated with oxygen and, therefore, so is arterial blood. B mismatch without HPV.
C mismatch with HPV. Blood flow to the poorly ventilated region is halved by HPV, increasing the ratio to 0. The lower blood flow through, and improved saturation from, this region means the Sa o 2 increases to almost normal.
D Worsening mismatch with HPV. Also, the P o 2 of mixed venous blood will now have a significant effect on the intensity of HPV and so Sa o 2. Assumptions made for the figure. As can be seen from figure 4, the concept of HPV simply diverting blood away from less well-ventilated regions is misleading.
Reducing blood flow through a region with low is helpful to reduce its effect on arterial P o 2 , but if ventilation to the region remains unchanged, then reduced blood flow also improves the ratio of that lung region and so the P o 2 of blood leaving it.
These theoretical considerations do seem to be relevant in vivo. Animal studies in which a region of lung is ventilated separately with hypoxic gas mixtures consistently show reduced perfusion to the region. The maximal effect seems to occur at alveolar P o 2 values from 25 to 50 mmHg; with severe hypoxia of less than 25 mmHg, HPV becomes less effective. Carbon dioxide must also be taken into account when considering the in vivo efficacy of HPV: as described in the Carbon Dioxide and pH section, both P co 2 and pH influence PVR, in particular, hypocapnia.
Fortunately, regional hypocapnia is unusual in clinical practice, and inadequate ventilation of a lung region normally results in increased rather than lowered P co 2. Also, as for oxygen, the P co 2 effect on HPV is determined by P co 2 of both alveolar gas and mixed venous blood, and the latter is unlikely to be reduced.
Thus, hypercapnia is unlikely to have a clinically significant effect on HPV, although avoidance of hypocapnia is advisable in situations where HPV is useful, for example, OLV. The contribution of HPV to matching in normal healthy subjects is controversial. However, despite recent theoretical evidence that vascular responses to oxygen are important in healthy humans, 31 numerous animal and some human studies using varied techniques have found little in vivo evidence of this.
Using the same methods as described in the previous paragraph, the answer seems to be yes. Chronic obstructive pulmonary disease COPD. Acute lung injury ALI. There is some evidence that HPV contributes to reducing the shunt fraction. For example, when diltiazem or intravenous nitrates are used to impair HPV, the shunt fraction increases, and when almitrine is used to enhance HPV, it reduces.
Altitude illness. If induced acutely, only modest levels of hypobaric hypoxia are required to stimulate HPV, and the cabin altitude of commercial aircraft is sufficient to induce an increase in PAP even in healthy subjects.
For these nonspecific catecholamines, this is in keeping with the presence of opposing receptors on pulmonary vessels. It must be remembered that in vivo these drugs are not specific for pulmonary vessels, being potent systemic vasoconstrictors, and so their ability to improve oxygenation in clinical situations is limited. A study using norepinephrine in patients with severe ALI found no improvement in oxygenation, a finding which the authors ascribed to the possibility of nonspecific diffuse vasoconstriction by norepinephrine.
These inconsistent reports illustrate the variability of the effects of catecholamines on HPV as a result of the multiple adrenoreceptors and the differing effects of catecholamines on pulmonary and systemic vessels. Animals studies show that at low doses almitrine enhances HPV 51 by a vasoconstrictor effect specific to pulmonary arteries. Its mechanism of action remains unknown although the effect is inhibited by nifedipine suggesting a calcium-mediated action.
Animal studies have demonstrated that at high doses, acetazolamide impairs HPV by a direct effect on PASMCs acting via an uncertain mechanism unrelated to its effects on carbonic anhydrase. Nitric oxide attenuates HPV by causing localized pulmonary vasodilation, and by administering nitric oxide via inhalation, relations may be improved. By this route, nitric oxide is only delivered to lung regions with some ventilation, and perfusion of these regions will therefore be enhanced. This is in effect providing a complementary strategy to that of HPV, that is, normoxic pulmonary vasodilation.
In some patients with severe ALI, nitric oxide inhalation alone, or in combination with systemic vasoconstriction using phenylephrine, may improve oxygenation by either improving matching or by increasing cardiac output. The lack of predictability in this context may be due to the heterogeneity of the lung pathological lesion in patients with ALI.
However, some patients, particularly those with pulmonary hypertension, may show an increase in Pa o 2 with inhaled nitric oxide during OLV.
Acute administration of intravenous methylprednisolone has no effect on HPV in dogs. Selective inhibitors of phosphodiesterase type 5 are now an established treatment option for pulmonary hypertension 62 and HAPE. Phosphodiesterase 5 inhibitors such as sildenafil impair the breakdown of cyclic guanosine monophosphate, which is responsible for the action of nitric oxide and other vasodilators in the PASMC.
As may be expected from drugs targeting the nitric oxide system, HPV is attenuated by both sodium nitroprusside and nitroglycerine. Hydralazine 65 is an inhibitor of HPV in humans at altitude, and there is evidence from a human study that sublingual nitroglycerine causes a small degree of hypoxemia which the authors ascribed to attenuated HPV.
Prostacyclin has potent pulmonary vasodilator properties and may be administered either intravenously or by inhalation. Intravenous prostacyclin is useful for treating pulmonary hypertension in critically ill patients, but its effects on the systemic circulation cause significant adverse effects.
Inhibition of the cyclooxygenase pathway by nonsteroidal antiinflammatory medications may decrease the production of prostacyclin and potentiate HPV. There has been one case report of the use of inhaled prostacyclin, in combination with systemic phenylephrine, to improve oxygenation during OLV. In animals, there is a dose-dependent reduction in HPV by verapamil 72 and nifedipine, 73 and similar findings have been reported with nifedipine in humans with COPD. Healthy subjects taking either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers have significantly reduced HPV.
Despite these physiological findings, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have been shown to reduce mortality in patients with COPD in the long term and after exacerbations, probably as a result of their immunomodulatory effects.
Which of the drugs is most effective for treating pulmonary hypertension remains uncertain. Many drugs used during anesthesia have an effect on HPV. Essentially any drug that is a vasodilator may inhibit HPV. All modern volatile anesthetic agents inhibit HPV in a dose-dependent manner. Halothane has been well studied and is a reasonably potent inhibitor of HPV. There does not seem to be any difference between the modern volatile anesthetics isoflurane, sevoflurane, 82 and desflurane 83 in their inhibition of HPV for equivalent MAC doses.
The common intravenous anesthetic agents show no inhibition of HPV. Even though propofol causes some systemic vasodilation, it does not inhibit HPV. Human clinical studies comparing arterial oxygenation during OLV with the newer volatile anesthetics versus intravenous anesthetics have generally not shown any significant difference. Unlike other current volatile anesthetics, nitrous oxide is not a vasodilator and seems to have pulmonary vasoconstrictive properties.
Animal studies have suggested some inhibition of HPV by nitrous oxide, 88 but this has not been reported in humans. Changes in chest wall and diaphragm shape, regional lung compliance, and artificial ventilation all contribute to abnormal matching during GA. Multiple inert gas elimination technique studies show that during GA, there are more areas of high and low fig. The variable effects of anesthetic agents on HPV described in the Effects of Anesthetic Drugs on HPV section indicate that there may be some impairment of the response but only at higher doses or with older agents.
Patients anesthetized with halothane or enflurane. Based on data from reference OLV is commonly performed to facilitate surgical access in the chest during lung, mediastinal, and intrathoracic esophageal surgery.
It is generally thought that the incidence of hypoxemia during OLV is decreasing. First, improved methods of lung isolation with the routine use of fiber-optic bronchoscopes to position double-lumen endotracheal tubes and bronchial blockers may lead to better ventilation during OLV and decreased risk of lobar obstruction; second, a better understanding of the physiology of OLV; and finally, improved anesthetic agents and techniques that cause less inhibition of HPV during OLV.
The high incidence of desaturation seen in studies of OLV from the s may be due in part to the use of halothane as the sole drug for maintenance of anesthesia. Similar to the pattern of HPV triggering by low P o 2 , the effects of the volatile agent on HPV are much more potent when delivered by the alveolus than by the mixed venous blood.
0コメント