by Isabelle PIOTROWSKI - Ghent...

GHENT UNIVERSITY

FACULTY OF VETERINARY MEDICINE

Academic year 2015 – 2016

The effects of mechanical ventilation on lung function in horses during anaesthesia

by

Isabelle PIOTROWSKI

Promotor: Dr. Stijn Schauvliege Literature Review

Co-promotor: Diego Rodrigo- Mocholi as part of the Master’s Dissertation

© 2016 Isabelle Piotrowski

Disclaimer

Universiteit Gent, its employees and/or students, give no warranty that the information provided

in this thesis is accurate or exhaustive, nor that the content of this thesis will not constitute or

result in any infringement of third-party rights.

Universiteit Gent, its employees and/or students do not accept any liability or responsibility for any use

which may be made of the content or information given in the thesis, nor for any reliance hich

may be placed on any advice or information provided in this thesis

.

GHENT UNIVERSITY

FACULTY OF VETERINARY MEDICINE

Academic year 2015 – 2016

The effects of mechanical ventilation on lung function in horses during anaesthesia

by

Isabelle PIOTROWSKI

Promotor: Dr. Stijn Schauvliege Literature Review

Co-promotor: Diego Rodrigo- Mocholi as part of the Master’s Dissertation

© 2016 Isabelle Piotrowski

FOREWORD:

First of all I would like to thank my promotor Doctor Stijn Schauvliege for giving me the opportunity to

work out this research topic and for his help and advice. I would also like to thank Diego Rodrigo-

Mocholi, for his useful tips and reading my literature study. Secondly, I am grateful to my friend

Alexander Füßinger for his support and understanding while working on this literature study, and also

to Caroline Liddell for improving my thesis and her motivational words. Finally, I would like to thank my

parents for enabling me to study and their support throughout my education.

ENGLISH SUMMARY 1

DUTCH SUMMARY 2

ABBREVIATIONS OF TERMS 4

INTRODUCTION 6

LITERATURE STUDY 7

1. Anatomy of the lungs 7

2. Gas exchange 7

2.1 Physiology 7

2.1.1 Ventilation 7

2.1.2 Perfusion 8

2.1.3 Ventilation Perfusion ratio 9

3. The effects of general anaesthesia and recumbency on lung function 9

3.1 Hypoventilation 9

3.1.1 Drug induced hypoventilation 9

3.1.1.1 Inhalation anesthesia 9

3.1.1.1.1 Isoflurane 9

3.1.1.1.2 Sevoflurane 10

3.1.1.2 Injectable anesthesia 11

3.1.2 Mechanically induced hypoventilation 11

3.1.3 Atelectasis 12

3.1.3.1 Absorption atelectasis 13

3.1.3.2 Compression atelectasis 13

3.1.3.3 Loss-of-surfactant atelectasis 14

3.2 Ventilation perfusion mismatch 14

3.2.1 0 < V/Q < 1 and V/Q > 1

3.2.2 V/Q = 0 14

4. Measures to improve lung function during general anaesthesia 15

4.1 Mechanical ventilation 15

4.1.1 Assisted ventilation 15

4.1.2 IPPV 16

4.1.3 PEEP 16

4.1.4 CPAP 17

4.1.5 Open lung concept 18

4.2 Positive effects of mechanical ventilation 19

4.2.1 Prevention of atelectasis 19

4.2.2 Reopen collapsed alveoli 21

4.3 Negative effects of mechanical ventilation 22

4.3.1 Cardiovascular effects 22

4.3.2 Barotrauma 23

DISCUSSION 24

REFERENCES 25

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ENGLISH SUMMARY

General anaesthesia in horses is associated with a number of complications such as hypoventilation,

hypercapnia and respiratory acidosis. The combined effects of anesthetic drugs and recumbency

impair the lung function during equine anaesthesia. Anesthetic drugs are dose-dependent depressants

that inhibit respiratory function by suppressing the normal compensatory mechanisms of breathing. In

recumbent horses the normal movement of the chest wall is restricted and the abdominal organs press

against the diaphragm, causing compression of large parts of the lungs. This results in hypoventilation

and insufficient tissue oxygen supply. Mechanical ventilation is often necessary to maintain adequate

respiratory function. Different ventilation strategies can be applied, which all aim to create a mean

positive intrathoracic pressure leading to increased cardiovascular system dysfunction. Intermittent

positive pressure ventilation in horses during general anaesthesia causes a decrease in heart rate.

During the use of positive end - expiratory pressure cardiac output decreases and the alveoli may be

overstretched by an excessive tidal volume causing barotrauma.

Besides the cardio-pulmonary impairments mechanical ventilation can improve pulmonary gas

exchange by reducing the formation of atelectasis. The application of the open lung concept technique

can reduce or prevent atelectasis and optimize oxygenation.

Because of the high susceptibility of horses for hypercapnia and hypoxaemia, mechanical ventilation

during general anesthesia is crucial for optimal anaesthetic management. Continued research into the

development of new and effective ventilatory strategies is needed to further reduce the negative

cardiovascular effects of anaesthetic drugs and to maintain lung function during general anaesthesia

in horses.

Key words: Anaesthesia – Gas exchange – Horse – Lung – Mechanical Ventilation

2

DUTCH SUMMARY

Met een sterftepercentage van 1,6 % is de anesthesie bij paarden in vergelijking met andere

diersoorten en de mens (anesthesie gerelateerde motiliteit 0,0001 %) met een veel hoger risico

verbonden. Hiervoor zijn verschillende redenen. De anesthetica hebben een onderdrukkende werking

op het ademhalingssysteem en de normale compensatoire mechanismen. De gevolgen zijn een

stijging van de arteriële partiele druk van koolstofdioxide (PaCO2) boven de 45 mmHg (normocapnie

40 – 45 mmHg) met hypercapnie en respiratoire acidose tot gevolg. Daarnaast wordt de ademhaling

onder algemene anesthesie van een paard in decubitus nadelig beïnvloed door de buikorganen die

tegen het diafragma drukken en het longvolume voor gasuitwisseling doet dalen. Het resultaat is

hypoventilatie met als consequentie een ontoereikende zuurstofvoorziening van de weefsels.

Verschillende types van geavanceerde ventilatoren werden ontworpen om ademhalingsondersteuning

te bieden aan paarden tijdens de anesthesie. De ventilatietechnieken gebruiken positieve druk om het

longvolume te vergroten en het ontstaan van atelectase te voorkomen. De gemiddelde druk in de

thorax wordt positief, waardoor de veneuze retour en het hartminuutvolume dalen. Uiteindelijk

vermindert de arteriële partiele zuurstofdruk (PaO2) (= arteriële hypoxemie). Afhankelijk van de

beademingsmodus is de impact op het cardiopulmonair systeem meer of minder uitgesproken.

Met intermitterende positieve druk ventilatie (Engels: Intermittent positive pressure ventilation of IPPV)

kan de PaCO2 binnen normale klinische grenzen gehandhaafd worden. De door compressie

veroorzaakte alveolaire collaps in onderliggende longgebieden kan echter niet vermeden worden met

IPPV. Bovendien ziet men een negatief effect op het cardiovasculaire stelsel, met een daling van het

hartminuutvolume tot gevolg.

Een andere methode om paarden tijdens de anesthesie mechanisch te ventileren is door het gebruik

van een positief eind – expiratoire druk (Engels: Positive end - expiratory pressure of PEEP) in

combinatie met het kunstmatig beademen van de longen. Het doel is collaps van alveoli te

verhinderen en de eerder atelectatische alveoli open te houden na een recruitment maneuver. Zoals

IPPV heeft PEEP een inhiberende werking op de cardiovasculaire functie, resulterend in een gedaald

zuurstoftransport naar de weefsels. Door een te grote drukamplitude zou het tot overexpansie van de

alveoli kunnen komen, met beschadiging van het longparenchym, waardoor de longfunctie

verslechtert. Deze ontwikkeling wordt ook wel barotrauma genoemd.

Tijdens de continue positieve luchtwegdruk (Engels: Continuous positive airway pressure of CPAP)

beademing wordt een positieve ademwegdruk doorheen de hele ademhalingscyclus gehandhaafd,

terwijl het paard zelfstandig ademt. Het zou de PaO2 in paarden tijdens de anesthesie verhogen en

bijgevolg de zuurstofvoorziening verbeteren, maar een cardiovasculaire depressie werd

gerapporteerd.

Een andere techniek van mechanische ventilatie beschreven in deze literatuurstudie is de open long

techniek (Engels: Open lung concept of OLC). Hier worden atelectatische longgebieden via een

recruitment manoeuvre heropend en het opnieuw collaberen van alveoli voorkomen door het

toedienen van een voldoende positieve druk. Aangezien gestoorde gasuitwisseling bij paarden tijdens

algemene anesthesie grotendeels gebaseerd is op de vorming van atelectase is de toepassing van

OLC een goede techniek om deze problematiek te voorkomen.

Mechanische ventilatie bij paarden tijdens algemene anesthesie is van cruciaal belang om

hypercapnie en hypoxemie te behandelen en om een optimale gasuitwisseling te garanderen. Verder

3

onderzoek naar nieuwe en effectieve beademingsstrategieën zijn nodig om de negatieve

cardiopulmonaire effecten te verminderen en om de longfunctie voldoende te onderhouden.

Sleutelwoorden: Anesthesie – Gasuitwisseling – Long – Mechanische Ventilatie - Paard

4

ABBREVIATIONS OF TERMS:

Abbreviation Term

ATP Adenosine triphosphate

CI Cardiac index

CO Cardiac output

CO2 Carbon dioxide

CPAP Continuous positive airway pressure

CPS Calculated pulmonary shunt

dAP Diastolic arterial blood pressure

fR Respiratory rate

FRC Functional residual capacity

HPV Hypoxic pulmonary vasoconstriction

HR Heart rate

IPPV Intermittent positive pressure ventilation

MAC Minimum alveolar concentration

MABP Mean arterial blood pressure

MLBP-TIVA Medetomidine, lidocaine, butorphanol and

propofol for total intravenous anaesthesia

MPAP Mean pulmonary arterial pressure

MRAP Mean right atrial pressure

OLC Open lung concept

Oxygen O2

P(A-a)O2 Alveolar-to-arterial oxygen tension difference

pAP Pulmonary arterial pressure

PaCO2 Arterial partial pressure of carbon dioxide

PaO2 Arterial partial pressure of oxygen

PACO2 Alveolar carbon dioxide tension

PAO2 Alveolar oxygen tension

PAOP Pulmonary arterial occlusion pressure

PAP Physiological airway pressure

PCO2 Carbon dioxide tension

PEEP Positive end - expiratory pressure

Q Perfusion

Qs/Qt Intrapulmonary shunt fraction

QT Total body blood flow

R Vasculare resistance

SAP Systolic arterial blood pressure

SMV Selective mechanical ventilation

SV Stroke volume

TIVA Total intravenous anesthesia

5

V Ventilation

A Alveolar minute ventilation

VDALV Alveolar dead space

VDANAT Anatomic dead space

VDPHYS Physiological dead space

VT Tidal volume

6

INTRODUCTION:

Mechanical ventilation in horses has been recorded since the beginning of the nineteenth century.

With the introduction of general anaesthesia in horses the suppressive effect of the anaesthetic drugs

on the respiratory system became significant.1 Different types of sophisticated large animal ventilators

were designed and the use of mechanical ventilation to provide ventilatory support during equine

anesthesia became common.2

Anaesthesia in horses carries a higher risk of mortality compared with small domestic animals and

humans. The overall death rate during general anesthesia in horses is up to 1,6%.3

One death in 100

is poor in comparison with the perioperative mortality rate in man, less than 1:10 000,4 and in

companion animals, 1:700.5

There are several reasons. When horses are anesthetized and become

recumbent, the volume and conformation of the rib cage changes and lung volumes are reduced.6

This reduction and the accompanying changes of the respiratory mechanics interfere with

maintenance of normal ventilation. Hypoventilation results and causes the arterial carbon dioxide

partial pressure (PaCO2) to increase. Moreover, the normal regulatory respiratory compensation

mechanisms are depressed by anesthetic drugs.

Although today mechanical ventilation of horses is a common procedure, its appropriate use needs the

recognition of the fact that applying positive pressure in recumbent horses is in a sense an

“unphysiological” challenge. When spontaneous ventilation is substituted by mechanical ventilation,

mean intrathoracic pressure becomes positive to an extent, which depends on the particular

characteristics of the implemented ventilation mode, and directly influences venous return and cardiac

output, which likely decrease. Also, the increase in intrathoracic pressure may force more pulmonary

blood into atelectatic lung regions and so increases the pulmonary shunt fraction and ultimately

decrease the arterial partial pressure of oxygen (PaO2) causing hypoxemia.2

The mechanical ventilation of horses during anaesthesia is necessary to treat hypoventilation and the

ensuing hypercapnia and respiratory acidosis.6 However, modern versatile ventilators and

investigations of new ventilatory strategies are needed to avoid respiratory and cardiovascular

dysfunction caused by mechanical ventilation.2

7

LITERATURE STUDY

1. ANATOMY OF THE LUNGS

Horse lungs are incompletely divided into lobes. The left lung is comprised of a cranial and a caudal

lobe. The right lung is larger than the left one because of an additional accessory lobe. In the standing

horse, a large portion of the lung lies dorsal to the diaphragm. From the dorsal perspective both lungs

have a similar configuration and reflect the general shape of the thoracic cavity. Fibrous connective

tissue separates the lung into lobules.7 This separation limits the collateral movement of air between

the different lung regions.8,9

Air is carried to the alveoli through the following structures: the nares, nasal cavity, pharynx, larynx,

trachea, bronchi, and bronchioles. The alveolar ducts and alveoli, in which gas exchange with blood

takes place, are connected with the small bronchi via bronchioles. Unlike some other mammals,

horses have no respiratory bronchioles.

The lung uses two sources of blood supply – the pulmonary circulation and the bronchial circulation.

The alveolar ducts and alveoli are coated in a comprehensive pulmonary capillary network to create a

huge surface area for gas exchange. Deoxygenated and carbon dioxide rich blood from the right

ventricle reaches the pulmonary capillaries via the pulmonary arteries. Through the pulmonary veins

oxygenated blood returns to the left atrium. This circuit is called the pulmonary circulation.

The complementary bronchial circulation is responsible for the delivery of nutrients and is part of the

systemic circulation.7

2% of cardiac output enters this circuit.10

A second important function of the

bronchial circulation is to warm up and humidify incoming air. Pulmonary arteries tend to be aligned

with the bronchial tree. However, some veins pass through the lung tissue independently of the track

of the airways and arteries. The bronchi and arteries are surrounded by a loose connective-tissue

sheath creating a bronchovascular bundle which also includes lymphatics and nerves.7

2. GAS EXCHANGE

2.1 PHYSIOLOGY

2.1.1 Ventilation

As aerobic organisms, horses depend on oxygen (O2) to produce sufficient adenosine triphosphate

(ATP) in the Krebs cycle. ATP is an immediately available energy source in cells and an important

regulator of energy delivering processes.

Good ventilation is required to deliver O2 used for energy production and to remove carbon dioxide

(CO2) from the blood.11

This includes the ability to transport air from outside the horse to the alveoli,

where gas exchange takes place.12

To ensure an adequate gas exchange the alveolar oxygen tension

(PAO2) has to be notably greater than the O2 tension in the pulmonary capillary blood. Otherwise, no

constant diffusion of O2 to the blood stream is guaranteed. In the opposite direction, the alveolar

carbon dioxide tension (PACO2) has to be lower than in the pulmonary blood stream to provide a

constant CO2 diffusion across the alveolar capillary wall.

Not the entire amount of inhaled air reaches the alveoli and contributes to gas exchange.11

About 50%

of the volume of gas entering the lung during inspiration remains in the conducting airways and is

8

exhaled unchanged.13

The only purpose of these regions of the upper respiratory tract is the transport

of gas to the alveoli. All the gas in the conducting airways which is still present after inhalation is part

of the anatomic dead space (VDANAT). The alveolar dead space (VDALV) represents the inspired air in

non - perfused alveoli. This air also doesn’t contribute to gas exchange. VDANAT and VDALV together

constitute the physiological dead space (VDPHYS):

VDPHYS = VDANAT + VDALV

An important parameter is the alveolar minute ventilation ( A) because of its relationship with blood

CO2 levels. It describes the volume of gas arriving in the alveoli per minute and is illustrated by the

following formula:

A = (VT – VDPHYS) x fR

fR is the respiratory rate11

and in a horse at rest is 10 – 12 breaths per minute.14

VT is the tidal volume

and describes the volume of gas entering the lung during inspiration.15

For the first studies of ventilation (V) and perfusion (Q) distribution in the lung researchers used the

steady-state inhalation and intravenous infusion of the 81mKr noble gas in healthy standing horses.16

Results indicated a vertical gradient of pulmonary V and Q. It seems that the dorsal part of the lung is

less ventilated and less perfused than the lower region. This finding agreed with the presumption that

the V and Q were affected by gravity.17

According to other researchers18,19

the V and Q distribution are well matched and independent of the

lung region. Thus, the influence of gravity on the V/Q distribution was questioned.

2.1.2 Perfusion

Q consist of the total body blood flow (QT) and vasculare resistance to blood flow (R) :

Q = QT / R

Blood volume, blood viscosity and the characteristics of the local blood vessels are also important

factors of Q.15

The lungs collect blood via the pulmonary and systemic circulation, which are arranged in series. The

total cardiac output from the right side of the heart flows through the pulmonary vessels. The main

function of the pulmonary circulation is gas exchange. The pulmonary trunk arises from the right

ventricle and carries venous blood to the lungs. It splits rapidly until a dense network of pulmonary

capillaries is created, where gas exchange takes place. Pulmonary veins then conduct the blood to the

left atrium. The bronchial circulation carries arterial blood and is responsible for the transport of

nutrients. Bronchial veins are absent and the venous return is taken over by the pulmonary veins or

the azygos vein.20

In 1964 researchers21

assumed that lung perfusion should be subservient to gravity. They

hypothesized that the dorsal pulmonary arterial pressure was lower than the ventral pulmonary arterial

pressure. Thus, the ventral lung areas were better supplied with blood compared to the upper parts.

9

In later studies the investigators16,22

refuted these findings. They used krypton perfusion, scintigraphy

and microspheres to analyze the pulmonary blood flow. The results indicated that gravity had no

influence on the distribution of blood flow in the equine lung. The study also indicated that the

caudodorsal lung regions were preferentially perfused.22

It should be noted that the sample size of this

study consisted of only four horses. A large part of the pulmonary blood flow is directed by hypoxic

pulmonary vasoconstriction (HPV). This concept prevents the perfusion of poorly ventilated lung

regions to ensure an efficient gas exchange. In the systemic circulation, hypoxia causes vasodilation.23

2.1.3 Ventilation Perfusion ratio

The ventilation perfusion ratio demonstrates how well these two factors are matched to each other in

the lung. For an adequate gas exchange a ratio of 1:1 would be optimal.15

This situation can change

by general anesthesia resulting in alveolar dead space formation and/or venous admixture.24

If V/Q >

1, the alveoli are well ventilated but they are not perfused sufficiently. The opposite direction indicates

hypoventilated (V/Q < 1) or unventilated (V/Q = 0) alveoli, which are well supplied with blood. This V/Q

imbalance prevents an ideal gas exchange.15

3. THE EFFECTS OF GENERAL ANESTHESIA AND RECUMBENCY ON LUNG FUNCTION

3.1 HYPOVENTILATION

Hypoventilation is defined as a reduction of ventilation per unit time and can be caused by two factors

during general anesthesia. First, anesthetic drugs suppress respiratory function15

and the normal

compensatory mechanisms of breathing. The consequences are a rise of the arterial partial pressure

of carbon dioxide (PaCO2) above 45 mmHg25

, resulting in hypercapnia and respiratory acidosis.

2

Secondly, the recumbency of the horse has an influence on lung function. Horses are in a lying

position during anesthesia which results in a changing conformation of the thorax. The lung volume is

decreased6 as well as the volume of gas which is inhaled.

26 As a result normal respiratory ventilation

cannot be maintained.2

3.1.1 Drug induced hypoventilation

3.1.1.1 Inhalation anesthesia

3.1.1.1.1 Isoflurane:

Isoflurane is an inhalation anesthetic and must be absorbed through the lungs to enter the

bloodstream. Good alveolar ventilation is required in order to achieve a sufficient concentration of

anesthetic in the blood for an adequate depth of anesthesia. Isoflurane is a fat soluble drug capable of

crossing the blood brain barrier.2 In this way isoflurane causes a suppression of the central respiratory

centers in the pons and medulla oblongata. The respiratory depression decreases the inhaled minute

volume in anesthetized spontaneously breathing horses.27

Other studies28,29

have shown that the fR

decreases but the VT is maintained or even increased during general anesthesia with isoflurane.

Furthermore, prolonged periods of apnea occurred in horses anesthetized with isoflurane in 100%

O2.28,29,30

10

Horses under general anesthesia cannot compensate for these changes because the drugs inhibit the

regulating mechanisms. The physiological response to hypoxia is HPV. In presence of hypoxia

pulmonary arteries constrict to reduce the flow of desaturated blood through underventilated areas of

the lung, to prevent inefficient gas exchange.31

Isoflurane depresses the HPV response by 50% at two

times minimum alveolar concentration (MAC).32

The MAC is defined as the alveolar concentration of an inhalation anesthetic at which 50% of the

patients no longer respond to a skin incision. Thus, it is a measure of the potency of an inhalation

drug.33

The lower the required MAC, the more potent it is. Isoflurane has a MAC value of 1,3%

compared to sevoflurane, which has a MAC value of 2,8% and is thus half as potent as isoflurane.34

Therefore, it is assumed that isoflurane has a smaller influence on the pulmonary function than

sevoflurane because the drugs are dose-dependent respiratory depressants.35

3.1.1.1.2 Sevoflurane:

Sevoflurane is also used to maintain anesthesia and leads to dose-related respiratory depression. The

negative effect on breathing is caused by central depression of medullary respiratory neurons,36

depression of diaphragmatic function37

and contractility.38

The blood solubility of sevoflurane is lower than that of isoflurane. Thus, after the end of anesthesia, a

faster elimination of sevoflurane compared to isoflurane is normally expected and consequently, a

shorter and possibly better recovery.39

This thesis has been partly refuted in a study in which 8 healthy

adult horses were anesthetized for two hours with 1.2 times MAC isoflurane or sevoflurane. Via

endotracheal tube insufflation 100% O2 or a certified standard gas mixture containing either 5% or

10% CO2 in O2 administered. During the first minute of recovery horses anesthetized with sevoflurane

had only half the fR compared to horses anesthetized with isoflurane. The alveolar ventilation was

decreased resulting in hypoventilation and higher values of carbon dioxide tension (PCO2). This

phenomenon was present for at least the first ten minutes after anesthetic recovery (Table 1).

Sevoflurane compared to isoflurane is characterized by a shorter terminal elimination half-life and in

addition to lower blood solubility it is removed more rapidly from the body.40

These properties should

improve the recovery but older studies41,42

have shown that sevoflurane causes more dose-dependent

hypoventilation than isoflurane, resulting in decreased alveolar ventilation and lower drug washout.

Thus the time of recovery is prolonged.

Table 1: Respiratory rate (fR) and carbon dioxide tension (PCO2) in eight horses recovering from 1.2 isoflurane or sevoflurane during insufflation without CO2 (to Brosnan B.J., Steffey E.P., Escobar A., 2012)

Measurement Iso 0% CO2 Sevo 0% CO2

0–1 minutes

fR (minute -1

) 4 ± 2 2 ± 1

PCO2 (mmHg) 68 ± 13 76 ± 7

5 minutes

PCO2 (mmHg) 52 ± 14 70 ± 10

10 minutes

PCO2 (mmHg) 54 ± 5 60 ± 6

11

3.1.1.2 Injectable anesthesia

Total intravenous anesthesia (TIVA) is simple to administer and does not require complex equipment.

Mostly, in TIVA, combinations of drugs are used to get an appropriate anesthetic effect. Xylazine,

detomidine and romifidine have a sedative-analgesic action. They are often combined with drugs such

as guaifenesin, diazepam, zolazepam, temazepam and climazolam, which cause muscle relaxation,

and dissociative anesthetics, such as ketamine and tiletamine.43,44

The extent to which the

cardiopulmonary system will be affected depends on the composition of the preparations and the

dose.2

Several studies43,45,46

have established that respiratory function is adversely affected. The

consequence is hypoventilation leading to hypoxemia with a PaO2 < 60 mmHg and hypercapnia with

a PaCO2 > 50 mmHg. Additionally, intrapulmonary shunting and V/Q mismatching also have an impact

on reducing the PaO2 values.47

Based on cardiopulmonary, endocrine and economic data other studies have suggested that TIVA

compared to inhalant anesthesia may be a better method to anaesthetize horses.48,49,50

3.1.2 Mechanically induced hypoventilation

Hypoventilation is caused by the combined effects of the anesthetic drugs and recumbency.51

During

general anesthesia horses are placed in a lateral, dorsal or sternal position. The abdominal organs

press against the diaphragm causing compression of large parts of the lungs 2 (Figure 1).

Fig. 1: The horse in dorsal recumbency, illustrating the relationship between the lungs, diaphragm and

abdominal organs. Note how the slanting diaphragm allows the abdominal contents to encroach on

the diaphragmatic lobes of the lung. Redrawn on the basis of x-ray studies by McDonell, Hall and

Jeffcott (1979). 1 = Heart; 2 = stomach; 3 = dorsal colon; 4 = ventral colon; 5 = caecum.53

The consequence is hypoventilation resulting in an increase of PaCO2.51

To examine the effect of body position on the cardiovascular and respiratory system 6 ponies were

trained to lie down for 30 minutes in lateral recumbency. It was seen that the PaO2 and PaCO2 values

did not change from the standing to the lying position, but in ponies with a higher body weight, lower

PaO2 values were measured after 10 minutes of recumbency. The authors concluded that ventilation

impairment during the first 30 minutes of general anesthesia is drug induced and not caused by the

body position.52

12

Other studies indicate a relationship between body position and the cardiovascular and respiratory

system. Thoracic radiographs of anaesthetized ponies in lateral and dorsal recumbency showed a

decrease in the dependent (lower) lung volume.53

This finding coincided with measurements of the

PAO2 and PaO2. Horses in dorsal and lateral recumbency have large differences between PAO2 and

PaO2, also called alveolar-to-arterial oxygen tension difference (P(A-a)O2), which is in contrast to horses

in sternal recumbency.54

It has also been shown that mechanical breathing impairment leads to a reduction of the functional

residual capacity (FRC). FRC is defined as the volume of air present in the lung after a normal,

passive exhalation. It serves as a physiological reserve of the lung. In recumbent horses the normal

movement of the chest wall is restricted and therefore FRC is reduced. In addition, FRC is even more

reduced by the cranial shift of the diaphragm. Beneath a certain reduction of FRC, airway closure and

alveolar collapse occur. The bases of the lungs are still well perfused but they are under ventilated.

This leads to ventilation-perfusion mismatch and favors the formation of compression and absorption

atelectasis. This ultimately leads to hypoxemia.

These mechanical changes result in a decreased compliance of the chest wall and lung and an

increased flow resistance with insufficient oxygen supply.32

3.1.3 Atelectasis

Atelectasis is an important cause of inadequate gas exchange during general anesthesia and is

induced by alveolar collapse.55

In early radiographic studies researchers have seen opacities in the lower lung areas of anesthetized

laterally recumbent horses.56

It should be mentioned that only very pronounced atelectasis can be

seen on conventional chest radiographs, but through the use of computer tomography (CT) scans the

findings acquired in the past have been confirmed.57

In a study carried out in 198558

, crest-shaped

increases in density were detected in the dependent regions of both lungs 5 minutes after the

induction of anesthesia in humans (Figure 2).

Fig. 2: Examples of CT scans of a human patient with healthy lungs, before and after induction of

anaesthesia. The CT slices are 1 cm above the level of the right diaphragm. Arrows indicate lung

densities, thought to represent atelectasis (from Rusca and colleagues).59

13

The evaluation of histological preparations of frozen lung tissue has revealed that the upper lungs are

well expanded while the lower lung regions present with atelectasis and large alveolar capillaries.

Based on these findings, it seems likely that alveolar collapse and vascular congestion occur during

general anesthesia in the recumbent horse.60

Almost 90 % of all anaesthetized patients developed pulmonary atelectasis in the most dependent

parts of the lung.57

This pathology occurs regardless of the method of anaesthesia (inhalant

anesthesia or TIVA) and breathing method (spontaneously or mechanically ventilated).61

Pulmonary

atelectasis can be classified into three categories: absorption atelectasis, compression atelectasis and

loss-of-surfactant atelectasis.

3.1.3.1 Absorption atelectasis

Absorption atelectasis may be caused by a complete airway obstruction, whereby gas is trapped in the

alveoli. Gas uptake by venous blood continues regardless of the fact that no new gas enters the

alveolus. This situation creates collapse.62

Alternatively, alveolar collapse may occur if the inspired V/Q ratio is too low. The critical V/Q ratio

describes the point where the rate at which inspired gas entering the alveolus is exactly balanced by

gas uptake from the alveolus into the blood. If the inspired V/Q ratio is less than the critical V/Q ratio

the lung unit will collapse.

Both mechanisms are based on the fact that less gas reaches the alveolus than the amount that is

removed by uptake by blood.63

3.1.3.2 Compression atelectasis

General anaesthesia could negatively affect the muscle tone of the inspiratory muscles. When the

diaphragm is paralyzed or less contractile, the abdominal pressure is more easily transmitted to the

thoracic cavity, which leads to lung compression.64

In a later study65

researchers used CT scans and detected altered diaphragmatic motions during

general anesthesia and mechanical ventilation. These findings were confirmed by further studies66,67

,

which detected changes in the end expiratory position of chest wall structures (Figure 3) and a

cephalad displacement of the most dorsal part of the diaphragm in horses during general anaesthesia.

14

Fig. 3: Diagram of a midsagittal section of the thorax while awake (solid lines) and while anaesthetized

(dashed lines). Note the alteration in the position of the diaphragm (cephalad motion in the dependent

portion; from Warner and colleagues).66

The researchers concluded that compression atelectasis during general anesthesia is caused by chest

wall configuration, diaphragm position and movement.

3.1.3.3 Loss-of-surfactant atelectasis

Loss-of-surfactant atelectasis occurs if the effect of the surface active agent is decreased such that the

surface tension of an alveolus increases.

It is possible that once atelectasis has formed, the function of surfactant is disrupted and the alveoli

collapse again after being reopened.68

3.2 VENTILATION PERFUSION MISMATCH

In the anaesthetized horse, V/Q mismatch represents the main cause of gas exchange

impairment resulting in a large P(A-a)O2 causing hypoxaemia, and is primarily due to alveolar dead

space and intrapulmonary right-to-left shunting.69

Recumbency and the anesthetic itself are largely

responsible for the inefficient gas exchange.55

3.2.1 0 < V/Q < 1 and V/Q > 1

In the lateral position, the volume of the dependent lung is clearly decreased and ventilation is

reduced to only one-fifth of the total ventilation.56

The perfusion of the dependent lung is also

reduced, but to a lesser degree than the ventilation, resulting in V/Q mismatch.60

In a study of 6 adult horses, with labelled microspheres, investigators found that the perfusion in

anaesthetized horses was preferentially distributed caudo-dorsally and evenly between the lungs

whether the horse was in lateral, dorsal or sternal recumbency. Meanwhile the distribution of

ventilation in the anaesthetized horses appears to depend on gravity with the uppermost part of the

lungs receiving the larger share. The poor V/Q ratio in anaesthetized and recumbent horses, could be

explained by the disassociation of ventilation from perfusion, in which the ventilation is preferentially

concentrated in the uppermost region of the lung, while perfusion is concentrated caudo-dorsally. That

would mean, that oxygenation is better in sternal than in lateral recumbency, and better in lateral than

in dorsal recumbency. This hypothesis was confirmed in the study.24

3.2.2 V/Q = 0

The term ‘pulmonary shunt’ represents blood that reaches the arterial system without passing through

ventilated regions of the lung (V/Q = 0).70

Based on the observations from a study in 2005, it is concluded that anatomical intrapulmonary

arteriovenous shunts of >15 μm in diameter, a potential cause of hypoxaemia when open, are not

present in horse lungs.71

Thus, pulmonary shunts could result from arteriovenous malformations,

venous drainage from bronchial arteries, venous drainage into the left ventricular cavity (Thebesian

veins) or the passage of blood past unventilated alveoli.72

15

Calculated pulmonary shunt (CPS) is used to investigate a global estimate of V/Q inequalities and

represents the percentage of Q that passes from the venous to arterial circulation without exposure to

ventilated alveoli to produce a given PaO2. In anaesthetized horses CPS values of 11 – 43 % are

reported to be associated with atelectasis. It is assumed to be the major cause of a decrease in PaO2

during anaesthesia, in combination with recumbency induced increases of dead space ventilation.54,73

In a study with 7 healthy Standardbred trotters, a correlation was seen between the development of

pulmonary shunts and recumbency of the horses during anaesthesia. The shunt was largest in dorsal

recumbency compared to the left lateral position, and the PaO2 was significantly lower in dorsal than in

left lateral recumbency, which suggests alveolar collapse due to compression. In the same study the

V/Q relationship was measured by the multiple inert gas elimination technique in conscious (standing)

horses, during halothane anaesthesia with spontaneous breathing, conventional mechanical

ventilation and selective mechanical ventilation, to evaluate among other things, shunt development.

The results have shown that in all 7 unsedated standing horses the V/Q ratio centered around 1, thus

the gas exchange is optimal. In addition a mean shunt of 1 % was observed. In the group

‘anaesthesia, dorsal recumbency with spontaneous breathing’, the average shunt fraction increased

up to 34 %. When the horses 1 - 4 were laterally recumbent, an average shunt of 20 % was measured,

thus significantly lower than in the previous group. Horses 2 – 5 were examined during dorsal

recumbency with conventional mechanical ventilation (CMV). No significant reduction in shunt was

noted, compared to spontaneous breathing in dorsal recumbency. In the last group (horses 2, 5 – 7),

selective PEEP of 20 – 30 cm H2O during selective mechanical ventilation (SMV) was applied, and

resulted in a decrease of shunt down to 13 % compared to horses during spontaneous breathing,

which could be explained by recruitment of collapsed lung.

The results indicate that the development of pulmonary shunt depends on recumbency and ventilation

technique (spontaneous versus mechanical ventilation). During anaesthesia compression atelectasis

occurs causing pulmonary shunts and finally generating hypoxaemia.69

4. MEASURES TO IMPROVE LUNG FUNCTION DURING GENERAL ANAESTHESIA

4.1 MECHANICAL VENTILATION

4.1.1 Assisted ventilation

During assisted ventilation, the horse initiates (‘triggers’) each breath through its own inspiratory

effort.2

Although different respirators use different triggering mechanisms, most often the breath is

initiated by a decrease in pressure.

During the inspiratory phase, the patient creates a negative pressure in the respiratory system, which

is registered as a breath. Depending on the settings of the respirator the breathing bag is then

compressed with a predetermined tidal volume. The expiration is caused by the retention force of the

lung. During assisted ventilation, the patient determines the inspiratory time and the respiratory

frequency.74

16

4.1.2 IPPV

Intermittent positive pressure ventilation (IPPV) is useful to compensate respiratory depression in

anaesthetized horses. During normal spontaneous breathing, intrapleural pressure ranges between –

10 cm H2O during inspiration and – 3 cm H2O at rest. The mean intrathoracic pressure is below the

existing atmospheric pressure. These properties are components of the respiratory pump and promote

venous return to the heart.75

If mechanical ventilation is used, intrapleural pressure values reach the

positive range, which reduces venous return to the heart and impairs cardiac output, possibly resulting

in a decrease in arterial systemic pressure and a reduction in O2 delivery.2,77,78

Even if IPPV is used

with oxygen–rich gas, the horse could become hypoxaemic.76

A more recent study has shown that the combination of IPPV and medetomidine, lidocaine,

butorphanol and propofol for total intravenous anaesthesia (MLBP-TIVA) can maintain cardiovascular

parameters within acceptable ranges (heart rate (HR): 29–31 beats/min, cardiac output (CO): 17–21

l/min, cardiac index: (CI) 36–46 ml/min/kg and stroke volume: (SV) 558–693 ml/beat). The horses

were anesthetized twice using MLBP-TIVA with or without IPPV at a 4-week interval. In each

occasion, the horses breathed 100% oxygen with spontaneous ventilation (SB-group, n = 5) or with

IPPV (CV-group, n = 5), and changes in cardiopulmonary parameters were observed for 120 minutes

at 20 minute intervals. The results showed no significant difference in mean arterial blood pressure

(MABP), mean right atrial pressure (MRAP) and mean pulmonary arterial pressure (MPAP) between

the groups. On the other hand, HR, CO, CI and SV were significantly lower in the CV-group compared

to the SB-group but not fall into apparent cardiovascular depression. The investigators concluded on

basis of the available parameters that horses anaesthetized with MLBP-TIVA preserved

cardiovascular function even in horses artificially ventilated with IPPV. However, the aforementioned

study is based on a low number of horses aged from 1 to 20 years. Thus, the results of the

cardiopulmonary parameters has been interpreted cautiously because of the significant decreases in

the HR, CO, CI and SV which were detected in the CV-group, compared to those in the SB-

group.79

Regardless of the negative effects of using IPPV, many studies have shown that the PaCO2 can be

maintained within normal clinical limits (PaCO2 of 40 – 45 mmHg) during IPPV.2,77,80

In this context, some researchers have described a potentially advantageous effect of moderate

hypercapnia in horses during anaesthesia, due to a sympathetic stimulation and vasoconstriction

which leads to an improved CO. However, a PaCO2 > 70 mmHg may result in myocardial depression,

arrhythmias and impairment of metabolism because of the concomitant respiratory acidosis, and

should not be exceeded.81,82

4.1.3 PEEP

Positive end - expiratory pressure (PEEP) can be added to spontaneous breathing or conventional

IPPV in horses during anesthesia.83

Two approaches can be used for this purpose: 1) Constant PEEP

during spontaneous breathing or IPPV.84

2) The titration of an incremental PEEP, in which PEEP is

progressively increased from zero, with a constant VT; or a decremental PEEP, with a high PEEP

level at onset and progressively reducing it with constant VT.84,85

The aim of PEEP is to prevent alveoli from collapsing and to maintain the previously atelectatic alveoli

open after a recruitment maneuver.86

17

Atelectasis is one cause of respiratory dysfunction and is especially significant in horses during dorsal

recumbency.69

It can result in arterial hypoxaemia even if an increased fractional inspired oxygen is

delivered and PaCO2 ranges between normal values.73

Furthermore the PaO2 has been actually

observed to decrease through the application of PEEP in a few studies in horses.69,87,88

In a more recent study on 13 isoflurane-anesthetized healthy horses, PEEP titration was performed by

increasing and decreasing the PEEP, in 5 cm H2O increments (from 5 up to 20 cm H2O) at 15 minute

intervals. The facial artery was catheterized to monitor arterial pressure and allow collection of blood

for pH and blood gas analysis (radiometer ABL 5; blood gas analyzer), such as, PaO2, PaCO2 P(A-a)O2.

The results of the study showed that an incremental PEEP titration sequence enhanced the pulmonary

gas exchange and lung compliance, whilst the decremental PEEP titration maintained good

oxygenation.84

In a study concerning 24 warmblood horses, a combination of IPPV and PEEP at 10 cm H2O resulted

in a better oxygenation when applied at the start of anaesthesia, compared to when IPPV was applied

without PEEP.83

Another study, in 6 adult horses, indicated that the use of a constant PEEP without recruitment

maneuver had a limited ability to reopen collapsed alveoli.89

Furthermore, if PEEP is used as sole

application it could lead to overexpansion of remaining well-ventilated alveoli and compression of

alveolar capillaries.90

Indeed, some studies showed, that PEEP can force blood to dependent, poorly ventilated but perfused

areas and so increase right-to-left pulmonary shunt of venous blood. Also, the increase in intrathoracic

pressure will impair the venous return, causing a negative effect on the CO.88,89

Nowadays, it is assumed that an immediate start of IPPV, combined with modest PEEP, could reduce

the incidence of atelectasis formation and thus represent a beneficial strategy to optimize gas

exchange in hemodynamically stable horses.2

4.1.4 CPAP

Continuous positive airway pressure (CPAP) is routinely used in human medicine to open or maintain

previously collapsed respiratory airways open by maintaining the airway pressure positively during the

entire respiratory cycle in spontaneously breathing patients.91

Previously, it was not possible to apply CPAP in horses because no adequate ventilator was available.

Recently, a new large animal ventilator driven by a servo-controlled piston can maintain a positive

airway pressure throughout the breathing cycle. The airway pressure can be kept constant in horses

by measuring the airway pressure in the region of the Y-piece and by computer controlled adjustment

of the piston position in spite of the high flow rates during expiration and inspiration.

In a case report, CPAP at a level of 20 cm H2O was used during anesthesia to treat hypoxaemia

during exploratory laparotomy in a horse with a diaphragmatic hernia. In this case, hypoxaemia was

treated successfully with CPAP, but a cardiovascular depression was reported.92

The findings are based on one horse and therefore no firm conclusions could be drawn regarding a

beneficial effect of CPAP, or adverse effects on the cardiovascular system.93

Another study, which unfortunately only included 5 horses, has also noted that CPAP might be able to

increase the PaO2 and therefore improve oxygenation in anaesthetized horses.28

18

In a recent study, 24 horses of different breeds were divided equally into two groups. In the first group

a CPAP of 8 cm H2O was applied to the airway system during anesthesia, whilst in the second group

no pressure was applied. The aim of the study was to compare the effects of CPAP on oxygenation

and ventilatory function during dorsal recumbency. A significant difference was found between both

groups for all ventilation parameters, and the degree of venous admixture / intrapulmonary shunt was

lower in the CPAP group.

This study also showed that CPAP improved oxygenation and maintained stable oxygen indices over

a period of 90 minutes in horses undergoing general anesthesia, without affecting the ventilatory

function negatively compared to the use of an atmospheric airway pressure. Although no conclusions

could be drawn concerning the influence of CPAP 8 cm H2O on venous return and cardiac output, it is

suspected that a higher CPAP level could be associated with increased cardiovascular system

dysfunction. Further studies have to be performed to analyze the correlation between CPAP level and

cardiovascular system function in horses.93

There are also some limitations93

, as seen in the previous two studies.92,94

First, only 6 horses from the

CPAP group and 3 horses from the physiological airway pressure group (PAP) finished the trial period,

which reduced the power of the analysis. Furthermore, trials must be constructed similarly to compare

studies.

Future studies with standardized methods over a longer time period and evaluating more specific

cardiovascular and respiratory variables, such as CO, pulmonary pressures, intrapulmonary shunt

fraction (Qs/Qt) and pulmonary dead space are required.93

4.1.5 OPEN LUNG CONCEPT

The open lung concept (OLC) strives to optimize gas exchange during anesthesia in horses with IPPV

through recruitment of atelectatic lung areas with recruitment maneuvers and preventing a new

collapse of the reopened lung areas by PEEP.95

One of the recruitment maneuvers utilized to “open up the lung” is to institute stepwise PEEP titration

and then keep the optimal PEEP value, which is the PEEP value that would sustain the benefits of the

recruitment maneuver.84

In a study in 30 horses, the influences of conventional IPPV and OLC were compared to each other in

relation to the cardiopulmonary system. The results showed significant differences between the groups

of the PaO2 measurements. The mean PO2 values were recorded as follows: For the OLC group,

horses registered values averaging between 300 and 400 mmHg PO2 during 25-95 minutes of

narcosis and again between 115-130 minutes. In the same time intervals, the IPPV group registered

significantly lower at 100-240 mmHg. (Figure 4).

19

Fig. 4: Comparison in horses (n = 30) of the PaO2 (average values) during anaesthesia of OLC -

ventilation and IPPV-ventilation; black bar = highly significant differences (p < 0,001). Translation:

arteriell = arterial; Narkosezeit = time of anaesthesia. (From Schürmann and colleagues, 2008).96

The high PaO2 level indicates an almost completely recruited lung and an undisturbed gas exchange

resulting in optimal oxygenation.

No significant differences in arterial blood pressure were found between the OLC and IPPV groups.

Only when recruitment maneuvers were being performed, the mean arterial blood pressure dropped

by up to 15 mmHg during 30 to 60 seconds in some cases. However, normal clinical values were

reached again after one minute. OLC seemed not to be disadvantageous in comparison to IPPV.

Further investigations with a larger number of patients have to be performed if OLC ventilation is

applied to reduce the rate of anaesthetic ventilatory side effects.96

4.3 POSITIVE EFFECTS OF MECHANICAL VENTILATION

4.3.1 Prevention of atelectasis

General anaesthesia and recumbency in horses is frequently accompanied by respiratory depression,

hypercapnia, hypoxemia and large P(A-a)O2. The disadvantageous impacts on pulmonary function

resulting in impaired gas exchange are mitigated by the use of mechanical ventilation during general

anaesthesia.97,98

In a study from 201099

, the hypothesis that an immediate start of IPPV provides better gas exchange

than a delayed start during inhalation anaesthesia in horses, was explored. This clinical approach was

based on 30 healthy warmblood horses positioned in lateral or dorsal recumbency. Horses of the first

group (n = 15) were ventilated immediately after induction. In the second group (n = 15) horses

breathed spontaneously for 40 minutes before IPPV was applied.

20

Arterial blood samples were taken at 20, 40 and 55 minutes after induction of anesthesia to analyze

PaO2 in mmHg, PaCO2 in mmHg and pH. P(A-a)O2 was calculated by the blood gas analyzer. At all

three measuring points the PaO2 values were higher, while the PaO2, P(A-a)O2 and alveolar dead space

fraction were significantly lower in the first group, compared to horses of the second group as shown in

Table 2.

Table 2: Mean values ± SD for PaO2, P(A-a)O2, PaCO2, calculated alveolar dead space fraction

(VDalv/VTalv), pH and mean arterial blood pressure of group I (immediate IPPV) and II (delayed IPPV).

*: Significant difference between group I and II.103

The alveolar dead space fraction was calculated

using following formula: VDalv/VTalv = (PaCO2-PE’ CO2/PaCO2) where PE’ CO2 is the end- expired

PCO2 and VT alveolar tidal volume.100,101,102

Variables Group T20 T40 T50

The results of this study showed a better gas exchange when horses underwent IPPV immediately

after the induction of general anaesthesia as compared to a delayed start after a period of

spontaneous breathing of 40 minutes. The measurements of the first group suggest that the

immediate start of IPPV could reduce the formation of atelectasis. Alveolar collapse in dependent lung

regions caused by compression of lung tissue cannot be avoided by IPPV. But alveolar collapse

caused by absorption of oxygen from alveoli in poorly ventilated lung units could be reduced because

IPPV increases ventilation in the dependent lung regions.

More studies are necessary to evaluate the influence of IPPV related to the prevention of atelectasis

during general anesthesia.99

PEEP titration is another mechanical ventilation technique to prevent the formation of atelectasis in

horses during general anaesthesia. Respiratory mechanical impairment could be treated in isoflurane

anaesthetized healthy horses by increasing and decreasing PEEP from 5 to 20 cm H2O at 15-minute

intervals. The results of the study84

showed that pulmonary gas exchange and lung compliance could

be improved by the use of incremental PEEP. At the incremental PEEP of 15 cm H2O, PaO2 increased

and P(A-a)O2 and physiological right-to-left shunt fraction decreased significantly which suggests that

21

the formation of atelectasis, which is thought to be the main reason for hypoxemia in healthy horses,

can be prevented. The optimal PEEP value to keep the atelectatic alveoli open was not exactly

established and should be figured out in order to use the method in a standardized manner.84

In five case reports of 2 horses and 3 ponies the hypothesis was established that CPAP of 10 cm H2O

may improve oxygenation during general anaesthesia. The horses and ponies were all positioned in

lateral recumbency and the anaesthesia were maintained with halothane. An arterial catheter was

placed into a facial artery for monitoring of arterial pressure and collection of blood samples. The

following parameters were continuously monitored (Tafonius and Datex-Ohmeda S5; Datex-Ohmeda

Finland OY, Helsinki, Finland) and recorded every five minutes to evaluate the impact of CPAP on the

cardiopulmonary system: heart rate (HR), systolic arterial blood pressure (sAP), diastolic arterial blood

pressure (dAP) and mean arterial blood pressures (MAP), end-tidal halothane concentration, end-tidal

CO2, expiratory tidal volume, fR, and minimal and maximal airway pressures.

In all cases the PaO2 increased which suggests that the application of CPAP could prevent the

formation of atelectasis.

It should be mentioned that the findings based on individual cases and the anesthetic protocols, time

of blood gas sampling, and duration of anesthesia were not standardized. Prospective clinical studies

and controlled records are necessary to confirm the results that CPAP may prevent alveolar collapse

and thus improve pulmonary gas exchange.94

4.3.2 Reopen collapsed alveoli

In 1992 the strategy of lung recruitment or OLC was first proposed for humans by Lachman and refers

to the dynamic process of opening previously collapsed lung units by increasing transpulmonary

pressure. The aim is to open all recruitable alveoli and adjust PEEP to keep them opened.103

The OLC

during anaesthesia consists of four following interventions (Figure 5).

1. Determination of the critical lung opening pressure

2. Determination of the minimal pressure that prevents the lung from collapsing

3. Active reopening manoeuvre by a brief increase in pressure

4. Keep the lung open by the lowest possible but still sufficient pressure

5. Continuous monitoring of blood gases as indicator of efficiency

6. If necessary repeat from step 3.

22

Fig. 5. Representation of the opening procedure for collapsed lungs. Note: the imperatives (!) mark the

treatment goal of each specific intervention. The bold words mark the achieved state of the lung. At

the beginning, the precise amount of collapsed lung tissue is not known. (Böhm et al. 1998)104

In a study of warmblood horses, which had been submitted to clinics for acute colic surgery, 30

individuals were divided into two randomized groups each consisting of 15 horses (control group

ventilated by IPPV versus OLC group). The recruitment of atelectatic lung regions occurs through the

use of recruitment manoeuvres in the form of intermittent increases of ventilation pressure with the aim

of expanding the lung volume in order to achieve a higher capacity for gas exchange. Re-collapsing of

the alveoli can be prevented by an individual PEEP. In this study PEEP values between 15 and 28 cm

H2O seem to be efficient to prevent alveolar re-collapse depending on patient and condtion.96

The PaO2 serves as global parameter to monitor a successful recruitment of the entire lung during

general anaesthesia.95

Evaluations of PaO2 showed significant differences between groups. The

mean values of the PaO2 of the OLC group ranged between 300 and 450 mmHg whereas in the

control group they ranged between 100 and 240 mmHg.

The present study showed that a significant improvement of oxygenation could be achieved by the use

of OLC compared to IPPV in horses during general anaesthesia in dorsal recumbency. Impaired gas

exchange in horses during general anaesthesia is largely based on atelectasis which can be reduced

or prevented through the application of the OLC technique.

It is necessary to use the OLC ventilation in a larger number of patients to conclude if this mechanical

ventilation technique is suitable to reduce the rate of anaesthetic incidents and recovery

complications.96

4.3 NEGATIVE EFFECTS OF MECHANICAL VENTILATION

4.3.1 Cardiovascular effects

Ventilatory support during general anesthesia in horses aims to treat hypoventilation, thus avoiding

hypercapnia and respiratory acidosis. But mechanical ventilation can affect cardio-vascular function

negatively.2

In a study of 10 healthy warmblood trotter horses, the effects of mechanical ventilation were compared

to spontaneous breathing with regard to the cardiovascular function. The horses were positioned in

dorsal recumbency and anesthesia were maintained with isoflurane. Horses in group 1 (n = 5) were

initially breathing spontaneously while horses in group 2 (n = 5) were initially mechanically ventilated

using IPPV by a large-animal pressure-controlled ‘bag-in-box’ ventilator (Stephen Ventilator;

Strömberg-Mika, München, Germany). After 2 hours of anaesthesia the method of ventilation was

changed. During anaesthesia, HR, CO, stroke volume (SV), systemic arterial blood pressures (SAP),

and pulmonary arterial pressure (pAP) were recorded to evaluate the negative cardiovascular side

effects. Blood gases such as PaO2 and PaCO2 were measured as well.

IPPV creates a positive intrathoracic pressure which reduces venous return to the heart, resulting in a

decreased CO.98

In addition, decreases in the PaCO2 during IPPV lower circulating catecholamine

levels and, therefore, sympathetic nervous stimulation of cardiovascular function.81

After changing the

23

method of ventilation from spontaneous breathing to IPPV, the HR decreased immediately, while

increased when IPPV was changed to spontaneous breathing.

The results showed that mechanical ventilation impaired cardiovascular function compared with

spontaneous breathing in horses during isoflurane anaesthesia. More studies involving a higher

number of horses are needed to elucidate the underlying mechanism.98

In a recent study, 13 isoflurane-anesthetized healthy horses were divided into two groups. In the

control group (n = 6) PEEP was maintained at 5 cm H2O during anaesthesia. In the PEEP group (n =

7) PEEP titration was performed by incrementally increasing and decreasing PEEP from 5 to 20 cm

H2O at 15 minutes intervals. All horses were recumbent dorsally. A 110-cm, 7.5F pulmonary artery

catheter (Swan Ganz; Edwards Lifesciences, CA, USA) was introduced aseptically and

percutaneously into the right jugular vein, so that its distal tip was located in the pulmonary artery for

measurement of CO, MPAP, pulmonary arterial occlusion pressure (PAOP), and central body

temperature. The CO was determined using the thermodilution technique at the end of expiration by

administering cold glucose solution (5%; 1 mL 15 kg ⁻1) into the right atrial catheter. The evaluation of

the hemodynamic parameters revealed that, in the PEEP group, at a PEEP of 20 cm H2O, the MPAP

and PAOP were respectively 30 and 42% higher than at baseline, while CO was significantly lower

compared to the control group (11%). The results of the present study showed a significant decrease

in CO at the highest PEEP level and thus a negative impairment of cardiovascular function.84

4.3.2 Barotrauma

Mechanical ventilation can damage the lung parenchyma especially if it is used inappropriately and

can result in barotrauma. It is characterized by over inflation and overstretching of the alveoli. It occurs

primarily during ventilation with excessive tidal volumes and a too large pressure amplitude between

inspiration and expiration.105,106

A barotrauma can lead to increased vascular filtration pressure, ruptures of the capillary endothelium,

the epithelium, the basal membrane and pulmonary fissures. This causes the penetration of liquid,

plasma and blood into the alveoli or air-conducting paths, and leakage of gas into the tissue.107

Surfactant is inactivated by plasma, resulting in a further deterioration of pulmonary function and

decreased compliance.108

In addition, shear forces occur between already collapsed alveoli and

immediately adjacent alveoli. They cause further injury of the pulmonary parenchyma. In an animal

model shear forces of up to 140 cm H2O between collapsed and adjacent ventilated lung regions could

be determined at a P peak of 30 cm H2O.109

24

DISCUSSION

Mechanical ventilation in horses during general anaesthesia is essential to ensure adequate tissue

oxygenation. Impaired gas exchange during anaesthesia is largely based on the formation of

atelectasis. As the results of this literature study show, IPPV is limited in its ability to counteract the

formation of atelectasis or reverse existing atelectasis. In contrast, OLC ventilation enables the

recruitment of collapsed alveoli. Also, adverse effects on arterial blood pressure occurs only very

sporadically and can be remedied within a short time through targeted adjustment of the ventilation

parameters. Meanwhile IPPV tends to cause a decreased cardiac output and has a suppressive effect

on cardiovascular function. However, these results should be considered critically due to the variation

in design of these diverse studies. Recumbency (dorsal, lateral or sternal), number of horses,

anaesthetic drugs and the length of the anaesthesia are only a few factors which have to be taken into

consideration. Furthermore, the various studies all evaluated different parameters using

measurements taken at inconsistent time intervals. To accurately compare between studies, all of

these elements have to be standardized.

PEEP can be applied via different methods, such as constant PEEP during spontaneous breathing or

IPPV, the titration of an incremental PEEP or a decremental PEEP. The aim is to prevent alveoli from

collapsing and to keep the previously atelectatic alveoli open after a recruitment maneuver. Many

studies with different approaches have been carried out to evaluate the influence of PEEP on the

cardiopulmonary system. The use of an incremental PEEP titration sequence was found to enhance

pulmonary gas exchange and lung compliance, whilst decremental PEEP titration maintained good

oxygenation. Meanwhile the use of a constant PEEP without any recruitment maneuver had a limited

ability to reopen collapsed alveoli and could lead to barotrauma. All the results of numerous studies

show a suppressive effect on the cardiovascular system caused by a positive intrathoracic pressure.

Regardless of the ventilation method PEEP cannot prevent hypoxaemia. Again the results must be

critically evaluated because of a lack of comparative studies which have the same methodology.

The advantages and disadvantages of the various ventilation options must be balanced depending on

the patient. A major point of criticism is that studies are mainly based on clinically healthy horses,

which is not the case in reality. Conditions such as colic or lung pathologies may change the

requirements for ventilation settings to guarantee an adequate gas exchange during general

anaesthesia.

Further research with standardized studies is necessary to develop better ventilation techniques with

lower negative cardiopulmonary impacts to decrease the mortality in horses during general

anaesthesia in the future.

Having evaluated a variety of methods, it seems that, OLC is the most promising ventilation method

for the future as it enables the reopening of atelectatic lung areas and can prevent re-collapse through

the application of an individual PEEP resulting in a sufficient oxygenation. What needs to be examined

more closely is the appropriate PEEP pressure. The pressure should be sufficiently high to keep the

alveoli open but also not so high that cardiovascular function becomes inadequate or lung

parenchyma damaged. To conclude, in comparison with other ventilation techniques OLC may have a

lower adversely hemodynamic affect thereby may decrease the risk of complications during equine

anaesthesia.

25

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