Research Request – Phrenic nerve pacing | FOI document library

FOI 24/25-0889 DOCUMENT 12

Research Request – Phrenic nerve pacing

Brief

Investigate and develop summary of available literature published including the below too:

• Information about the total phrenic nerve pacing support ‘package’ including equipment and interventions (hospitalisation, surgery etc) required to implement support, maintenance or replacement of equipment etc

• Any clinical guidelines available outlining potential risks and benefits of the Phrenic nerve pacing option, recommendations around the medical assessment/monitoring supports,

• What would be other support options considered/required instead of phrenic nerve pacing support? what alternative respiratory support options look like

Date: 12/06/2020

s47F - personal p [s47F - personal priv](/foi-library/releases/759e22e37354-foi-24-25-0593-decision-document/release-materials/material-001__s47f-personal-privacy/) Requester: Julie (Assistant Director), Karyn (Director)

s47F - personal priv Researcher: Jane (Research Team Leader)

s47F - personal priv Cleared by: Jane (Research Team Leader)

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision making.

Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice.

The Research Team are unable to ensure that the information listed below provides an accurate & up‐to‐date snapshot of these matters

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Contents

Summary …………………………………………………………………………………………………………….. 3
What is the phrenic nerve? ……………………………………………………………………………………. 4
What is phrenic nerve stimulation? ………………………………………………………………………… 4
Intra‐muscular diaphragm stimulation …………………………………………………………………….. 4

4.1 Literature Review ……………………………………………………………………………………………. 5

4.2 Experimental use in the treatment of amyotrophic lateral sclerosis ……………………….. 6

Phrenic nerve pacing via direct stimulation ……………………………………………………………… 6

5.1 Indications ……………………………………………………………………………………………………… 6

5.2 Patient selection ……………………………………………………………………………………………… 7

5.3 Benefits of phrenic nerve pacing ……………………………………………………………………….. 7

5.4 Surgical Information ………………………………………………………………………………………… 8

5.4.1 Thoracic approach ……………………………………………………………………………………… 9

5.4.2 Cervical approach…………………………………………………………………………………….. 10

5.5 Post‐operative care ……………………………………………………………………………………….. 10

5.6 Product warranty …………………………………………………………………………………………… 11

5.7 Device Failure/backup ……………………………………………………………………………………. 12

5.8 Number of implanted devices and long‐term follow up data ……………………………….. 13

5.9 Outcomes and Quality of Life ………………………………………………………………………….. 14

5.10 Cost Effectiveness ………………………………………………………………………………………… 16

5.11 Initial set up costs ………………………………………………………………………………………… 16

Comparative respiratory treatment options …………………………………………………………… 17

6.1 Position pressure ventilation …………………………………………………………………………… 17

6.1.1 Invasive ventilation (also known as mechanical ventilation) …………………………… 17

6.1.2 Non‐invasive ventilation …………………………………………………………………………… 18

6.2 Negative pressure ventilators ………………………………………………………………………….. 18

6.3 Additional respiratory supports ……………………………………………………………………….. 19

Reference List …………………………………………………………………………………………………….. 24

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Summary

Phrenic nerve stimulation is not a new concept and has been around for decades.

 The quality of evidence investigating phrenic nerve pacing is rated as low due to

small sample sizes, lack of comparison groups and high potential for bias.

o This is due to the low number of patients who meet the strict criteria for

surgery. For example, a report from the UK has estimated that only 4‐5

patients per year would be deemed suitable. Data from the Avery Biomedical

(first FDA approved device in 1987) shows that as of 2018 only 973 devices

have been implanted globally. This means that the procedure is also relatively

uncommon in other countries other than Australia (no MBS code for the

procedure or any mention in Insurance/compensation schemes).

o Although evidence is weak. The overall clinical consensus is that the

procedure is safe (low adverse events and no deaths linked to the procedure)

and there is long‐term follow up data that shows many patients have

continued to pace for over 10 years.

o No data which investigates whether the device increases life expectancy

o Improved comfort level, improved speech, reduced anxiety and

embarrassment, and reduced hospitalisation due to respiratory infections are

the several benefits of the device

 Cost effectiveness: no studies undertake a complete cost effectiveness analysis,

however, a UK report provide a basic 10 year comparison which found that

mechanical ventilation is slightly cheaper than phrenic nerve pacing. Those using

phrenic never pacing report greater quality of life and reduced hospitalisation from

respiratory tract infections which would likely offset these costs.

o Refer to section 5.6 and 5.7 for information on product warranty and device

failure of each component.

 Mechanical ventilation (invasive) is still the most common form of respiratory

support. Refer to section 6 for an overview of other respiratory supports.

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What is the phrenic nerve?

The body has two phrenic nerves, a left and a right one. Each originates in the neck and

passes down between the lung and heart to reach the diaphragm. These nerves play a

pivotal part in breathing – passing motor information to the diaphragm while receiving

sensory information.

What is phrenic nerve stimulation?

Phrenic nerve stimulation, also known as diaphragmatic pacing, is an alternative to standard

mechanical ventilation. The application of repetitive stimulus patterns to the phrenic nerves

causes smooth, rhythmic contractions of the diaphragm, which result in the inhalation of air

into the lungs.

There are 3 commercially available devices that can stimulate the diaphragm. The Mark IV

Breathing Pacemaker, made by Avery Biomedical Devices; the Atrotech OY’s Atrostim; and

the Synapse Biomedical NeuRx [1]. The Avery and the Synapse devices are available in the

United States, and the Atrotech device is available only in Europe. The Synapse NeuRx

device received FDA approval in 2011 for humanitarian use in patients 21 years or older

with amyotrophic lateral sclerosis (ALS). The Avery Mark IV Breathing Pacemaker received

full premarket approval by the FDA in 1987 and is reimbursed by Medicaid and Medicare

services in the USA. A key difference between the devices is that the Mark IV Breathing

Pacemaker and Atrotech OY’s Atrostim stimulate the phrenic nerve and the NeuRx DPS is an

intramuscular diaphragm stimulator. This is a newer approach which uses an abdominal

laparoscopic approach has been proposed instead, in an effort to reduce the risk of phrenic

nerve injury [2, 3].

The benefits of intra muscular diaphragm stimulators (NeuRx) for long‐term use following

spinal cord injury are questionable [4, 5].

Intra-muscular diaphragm stimulation

The aim of intramuscular diaphragm stimulation is to make the diaphragm contract,

strengthening it and allowing full or partial weaning from mechanical ventilation [5]. This

procedure needs intact phrenic nerve function, and avoids the need to access the phrenic

nerve through the neck or thorax, as well as reducing the risk of phrenic nerve damage [5].

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The procedure is done laparoscopically with the patient under general anaesthesia. A

special probe is used to identify areas of the diaphragm where minimal electrical stimulation

causes maximal diaphragm contraction (known as the ’motor points) [5]. Two intramuscular

electrodes are implanted on the abdominal surface of each hemi‐diaphragm at the motor

points. The electrode leads are tunnelled subcutaneously to an exit site in the chest where

they are connected to an external battery‐powered pulse generator [5]. A reference

electrode (anode) is also implanted and the leads tunnelled with the other electrodes.

Intraoperative stimulation and voltage calibration tests are carried out to confirm adequate

contraction of the diaphragm. After implantation the patient has a diaphragm conditioning

programme, which involves progressive use of the system for increasing periods of time

with gradual weaning from the ventilator [5].

4.1 Literature Review

A systematic review [6] of 148 patients with traumatic high cervical spinal injuries and

ventilator‐dependent respiratory failure (from 12 studies), intramuscular diaphragm

stimulation systems were implanted successfully in all patients except one. This was

because of a false positive preoperative phrenic nerve conduction test in this patient.

Half of the patients (range 40% to 72%) could be weaned from ventilators after the

procedure and most could use the stimulator instead of a ventilator for several hours per

day. One study [7] reported that more than 50% were using diaphragm pacing 24 hours per

day and up to 96% were able to use pacing for 4 hours continuously.

Current evidence on intramuscular diaphragm stimulation for ventilator‐dependent chronic

respiratory failure caused by high spinal cord injuries shows that there are serious but well‐

recognised safety concerns [4, 5] (see Table 1 for list of safety concerns). NICE guidelines [4,

5] report anecdotal evidence of increased mortality and decompensated respiratory failure

and breathlessness related to diaphragm pacing. Evidence on efficacy is limited in quantity

and quality. Therefore, the NICE recommends that this procedure should only be used in the

context of research.

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In comparison to standard phrenic nerve pacing devices, the intramuscular diaphragm

pacing machines do not have long term follow up/safety data (only 12 years compared to 45

for original phrenic nerve pacing devices), additional risk of infection due to protruding

wires, only a single point system failure meaning there is no backup if the system fails [4, 5,

8].

4.2 Experimental use in the treatment of amyotrophic lateral sclerosis

The Synapse Biomedical NeuRx has humanitarian approval for use in those with

amyotrophic lateral sclerosis (ALS) [2, 3]. Randomised controlled trials have shown

increased mortality in groups treated with NeuRx, although the reasons for this were

unclear [5]. Safety issues arising from studies included increased adverse and serious

adverse events, respiratory failure, capnothorax, venous thromboembolism, gastrostomy

tube placement, infection at the stimulation cable entry point was noted in 22%, and wire

failure was reported in 14% [4, 5].

NICE guidelines conclude that intra‐muscular diaphragm stimulation for motor neurone

disease poses serious long‐term safety concerns. Evidence on efficacy is limited and

therefore, this procedure should not be used to treat this condition. The peer reviewed

literature referenced in the NICE guidelines has not been summarised in this document but

can be found at https://www.nice.org.uk/Guidance/IPG593

At this time, there are no studies comparing phrenic nerve stimulation and intramuscular

diaphragm stimulation.

Phrenic nerve pacing via direct stimulation

5.1 Indications

A phrenic nerve pacer is indicated in persons who require chronic ventilator support

because of upper motor neuron respiratory muscle paralysis (RMP) or because of central

alveolar hypoventilation (CAH) and whose remaining phrenic nerve, lung and diaphragm

function is sufficient to accommodate electrical stimulation [9]. All ventilator dependent

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people with high spinal cord injury (C0‐C4) with intact phrenic nuclei should be considered

for this procedure, regardless of age or gender [10].

Candidates for diaphragm pacing include, but are not limited to, patients who have [9]:

 Central alveolar hypoventilation

 Decreased day or night ventilatory drive (i.e. sleep apnoea, Ondine’s curse)

 Brain stem injury or disease

 Spinal cord injury or disease

5.2 Patient selection

Diaphragm pacing is generally indicated in prospective candidates who have [9, 10]:

 Functional lungs and diaphragm muscle

 Intact or repaired phrenic nerves

 Absence of infection

 A clear and adequate upper airway (including nasopharynx, pharynx and larynx)

 Adequate physical caregiver quality and availability including nursing, family support

and medical care

5.3 Benefits of phrenic nerve pacing [11]

Subjective sense of more normal breathing

Improved comfort level

 Elimination of ventilator tubing

 Easier transport outside the home  Easier transfer to and from bed

 Increased mobility

Improved speech

Restoration of olfactory sensation

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Reduced anxiety and embarrassment

 Elimination of ventilator noise

 Elimination of ventilator tubing and fear of ventilator disconnection

 Daytime closure of tracheostomy

Reduced overall costs

 Reduction or elimination of ventilator supplies

 Reduced level of caregiver support

5.4 Surgical Information

The phrenic nerve pacing system consists of ‘implanted components’ (phrenic nerve

electrodes, implanted connector and radiofrequency receiver) and ‘exterior components’

(antenna and stimulus transmitted) which can be seen in Figure 1 [11].

A surgical procedure is necessary to implant the electrode under the phrenic nerve and the

receiver just under the surface of the skin [8]. This procedure can take place at the neck

(cervically) or in the chest (thoracically). Usually patients receive two sets of implants, one

on each side, unless their condition is limited to only one side [8, 11].

The procedure averages 2‐4 hours in length [8, 10]. Depending on the procedure selected, it

can be performed on an outpatient basis [8]. The decision as to which approach is

appropriate is determined by the surgeon performing the procedure [8, 10, 11].

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Figure 1. Basic design of commercially available phrenic nerve pacing systems. The internal components (right side of image) consist of a single electrode implanted on each phrenic nerve in the thorax; each electrode is connected by wires to subcutaneously implanted radio‐frequency receivers. The external components consist of a stimulus transmitter and attach rubberised antennae which must be positioned over the radio‐frequency receivers. The receiver converts them to electrical signals from the transmitter and converts them to electrical signals which stimulates the phrenic nerves to activate the diaphragm.

5.4.1 Thoracic approach

The thoracic approach involves a small (5‐7 cm) incision made between a pair of ribs so that

the phrenic nerve can be isolated alongside the heart. The surgeon places the electrode

under or near the phrenic nerve and sutures it in place. The receiver is then placed just

under the skin, usually from within the same incision [8, 10].

The thoracic approach can be performed in a minimally invasive manner by using video‐

assisted thoracic surgery techniques. Since a small camera is used to provide visualization of

the operative site, the incision can be significantly smaller [8, 10].

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The thoracic approach can also be performed thoracoscopically and involves the use of

multiple small (5‐10 mm) incisions instead of one primary incision. Through these incisions,

a camera and specially designed instruments are used to visualize the nerve and place the

electrode. Thoracoscopic procedures can be performed with standard endoscopic

instruments or by use of a surgical robot [8, 10].

This approach is commonly chosen for the youngest paediatric patients since the anatomy

of the neck is not sufficiently developed in these cases. It is also a common approach for

patients who are suspected of having nerve damage so that the stimulation can occur below

the presumed injury [8, 10].

5.4.2 Cervical approach

The cervical approach is also considered minimally invasive since it does not require a

thoracotomy, or chest procedure [8, 10].

It uses a small (3‐5 cm) incision made in the area where the neck meets the torso. The

phrenic nerve is isolated where it is most superficial. The surgeon places the electrode

under the phrenic nerve and sutures it in place. The receiver is then placed just under the

skin, usually within a small pocket made on the upper part of the chest [8, 10].

This approach is commonly chosen for older paediatric patients and adult patients who are

known to have good phrenic nerve conduction. In addition to avoiding a thoracotomy, this

approach has the advantage that it can be performed on an outpatient basis for some

patients [8, 10].

5.5 Post‐operative care

A report by the NHS [10] has suggested that an in‐patient stay (surgery, post‐surgical

recovery and phrenic conditioning) typically takes 12 weeks. Patient, family and

carers/nurses will be expected to attend the implanting centre to undertake training in the

on‐going use of the pacing controller (7 days). At the end of pacer surgery and conditioning

the person will return to their treating centre/home. For those returning to a spinal cord

injury centre, a guarantee of bed availability on completion of the procedure will be

required. Annual review of the system is undertaken for the first three years after surgery,

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requiring readmission on each occasion for a maximum of 2 days. The implanting centre will

provide further support through telephone, outreach and/or further out‐patient review as

required.

Immediate postoperative care should include:

 Maintenance of usual, chronic ventilatory support and/or pacing on an unaffected

side

 Continuation of intraoperative antibiotics for a reasonable period

 Use of a short postoperative course of steroids to diminish the incidence of

perineural oedema.

 Meticulous wound care to decrease infection

 The patient’s CO2 level should be in the mid to upper 30’s prior to pacing. If

necessary this level should be gradually adjusted during the 10‐14 day waiting

period [8, 10].

5.6 Product warranty

All warranty and information on device failure is taken from the Avery Biomedical website

[8].

Transmitter: 3 years

The expected service life of the Mark IV transmitter (Avery Biomedical) is 10 years. There is

no calibration, preventative or scheduled maintenance during the lifetime of the transmitter.

Antenna: 90 days

It is recommended that they are replaced every 6 months (expected service life). Proper care

and gentle handling will make them last longer but they will eventually wear out.

Receivers: 5 years

Receivers have an expected service life of 10 years. Replacement can be done under local

anaesthetic on an outpatient basis.

Electrodes: 5 years

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Most electrodes will serve the patient for their entire life. In rare instances electrodes have

been damaged or destroyed through stretching because of growth of the patient.

In cases of receiver replacement, with undisturbed electrodes, pacing can begin

immediately. With newly implanted electrodes, diaphragmatic pacing should be deferred in

the immediate postoperative period. Surgical trauma causes local perineural oedema and

oedema of the subcutaneous tissues. Healing, with fibrosis and accommodation gradually

occur and pacing can safely begin at about 10‐14 days postoperatively. However, some

doctors may choose to wait longer depending upon patient status.

Depending on patient status, discharge from the hospital following recovery from surgery is

suggested. The patient may then be brought back to the hospital or clinic for initiation of

pacing or may initiate pacing at home. Regardless of patient diagnosis, determination of

each hemidiaphragm threshold is required prior to the start of effective bilateral diaphragm

pacing. Threshold is the lowest transmitter amplitude setting that starts muscular

contraction.

5.7 Device Failure/backup

Failure of the diaphragm pacing system can occur due to battery failure, broken battery

connector wire, or intermittent antenna cable or connector, or component failure in the

receiver, electrode wire, or external transmitter. Avery Biomedical diaphragm pacing

systems are designed with bilateral redundancy for superior safety. Each diaphragm is paced

by its own receiver, electrode, and external transmitter output. This independence provides

an extra level of safety as there is no single failure point which could cause the entire

system to stop working. These devices have also been subject to rigorous environmental

and electromagnetic testing by independent laboratories to ensure safety and efficacy.

A device for providing artificial ventilation by mask, mouth piece or tracheal tube should be

available for those patients who are continually dependent on the phrenic pacemaker as an

alternative to mechanical ventilation.

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5.8 Number of implanted devices and long‐term follow up data

The UK national incidence and prevalence figures for spinal cord injury would indicate 40

newly injured patients per annum would require mechanical ventilation support [10]. Using

data from the single implant centre in the UK as a reference, 12% of these cases would likely

require lifelong invasive ventilation (whilst the remaining 88% would wean from

ventilation), and that 35% of this group (4‐5 people) would be suitable for phrenic nerve

implantation each year [10].

Recent data from Avery Biomedical [8] shows that a total of 973 (since 1970’s) active,

deceased, and inactive patients have been implanted with a phrenic nerve pacing device.

331 patients were implanted using the cervical approach, 630 using the thoracic approach,

and 12 using cervical for one side and thoracic on the other.

The majority (50%) of patients with a phrenic nerve pacer had a diagnosis of spinal cord

injury (Figure 2).

Figure 2. Graph of patients implanted per year separated by surgical approach.

Two patients have been pacing for 40 years. A total of 68 active patients have been using

the Avery Diaphragm pacer for over 30 years with an additional 9 patients who paced for

over 30 years before death. The average amount of time in between revisions for this group

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of patients was 15.1 years. Approximately 8% of patients (3 total) in this category required

no revisions since their original implantation (Figure 3) [8].

195 revision surgeries were identified in the company database [8]. 37 of 331 patients who

were initially implanted cervically and 78 of 630 patients initially implanted thoracically

required one or more revision surgeries. Of the 64 cervical implant revisions, 52 had no

change of electrode location and 12 had the electrodes moved into the thoracic region. Of

the 131 thoracic implant revisions, 126 had no change in the location of their electrode and

5 were moved into the cervical region [8].

Figure 3. Number of years spent using the Diaphragm Pacer as of November 2018.

5.9 Outcomes and Quality of Life

The main outcomes considered in the only published systematic review [12] on phrenic

nerve pacing were survival rates, complication and infection rates and quality of life

measures. Changes to speech were also assessed. The changes to quality of life and speech

were self‐reported.

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The best evidence comes from a non‐randomised comparative trial of 64 patients (32

managed by mechanical ventilation and 32 including phrenic nerve stimulation) [13]. There

was a trend towards improved survival with phrenic nerve stimulation, however, those

treated with phrenic nerve stimulation were younger, more likely to be male and the

difference was not statistically significant.

There was a statistically significant difference in the incidence of respiratory infection

between the two groups. Rates of respiratory infection were equivalent at baseline. The

study reported a median of 1.43 infections per 100 days of rehabilitation in the phrenic

nerve stimulation group compared with 1.33 in the mechanical ventilation group [13].

Following intervention the phrenic nerve stimulation group experienced no respiratory

infections (interquartile range 0 to 0.92) whereas the mechanical ventilator group had an

increased median rate of 2.07 infections per 100 days of rehabilitation (interquartile range

1.49 to 4.19) in the second phase of this study while both groups were institutionalised [13].

The main reason for premature death was respiratory complications. These occurred in 10

of the 14 deaths in the mechanical ventilator group and 3 of the 9 deaths in the phrenic

nerve stimulation group, this difference may be clinically important and statistically

significant, though the phrenic nerve stimulation group was younger [13]. It is not possible

from the evidence published to determine if phrenic nerve stimulation impacts on life

expectancy [10, 13].

Self‐reporting of symptoms by patient questionnaire and assessment by clinicians indicated

an improvement in quality of life and speech. Likely due to lower postoperative respiratory

infections in the group treated with phrenic nerve stimulation compared to the

mechanically ventilated group [10, 13].

Long‐term outcomes are reported in case series from France [14] and Australia [15]. These

suggest that a median of 13 years use is possible and that patients were able to achieve

tolerance of up to 24 hours continuous usage. 8 hours use is more frequently reported with

mechanical ventilation support through the night for some patients.

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5.10 Cost Effectiveness

Hirschfield, et al. 2008 [13] in a controlled study reported that the initial cost of the phrenic

nerve stimulation device was offset by reduced need for nursing care and a reduction in

treatment for respiratory infections within one year of implantation. The aim of phrenic

pacing is for 24 hours ventilator‐free breathing, however, Avery Biomedical reports that only

17% of patients pace for 24 hours per day [8]. Therefore, there is still a considerable cost

associated with nursing care of patients with phrenic nerve pacing devices. No other

publications were identified that reported on the costs or cost effectiveness of this device.

Khong, Lazzaro et al. 2010, [15] reported a number of device failures that required revision

surgery. These costs would need to be included in any cost effectiveness evaluations. In

addition part time use of phrenic nerve stimulation with the continued support of

mechanical ventilators would need to be accounted for in assessing the overall cost impact

of deploying the device.

The difference in equipment costs for establishing a person at home on 24 hour ventilation,

or 24 hour phrenic nerve pacing has been costed in an NHS report [10]. The initial outlay

and 10 year consumable costs are summarised below (converted to AUD from Pounds).

*Note, these prices are from 2014 and are likely to have increased.

5.11 Initial set up costs

Phrenic pacing (plus back‐up ventilator): $96,754.88

Ventilator dependent patient: $18,704.22

10 year equipment and consumable costs;

Phrenic pacing $16,878.72

Ventilator dependent patient %72004.42

Price differential over 10 years (per annum); $2,292.49

The additional cost for establishing a person on a phrenic pacing system is therefore

$2,292.49, but the impact on patient‐reported quality of life and increased life expectancy

would perhaps outweigh this slightly increased cost. The greatest cost saving relates to the

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impact of phrenic pacing on reducing respiratory infection. The Hirschfeld et al. [13] study

notes a significant reduction in respiratory infection rates for mechanical ventilation versus

phrenic paced cases (p<0.001). A single hospitalisation episode for respiratory infection in

this highly vulnerable patient group is lengthy and costly; chest infection without

consolidation (approximately 2‐4 weeks); with consolidation (approximately 4‐6 months).

Therefore whilst this cost remains unquantifiable, given the current level of evidence, the

potential cost saving and impact on patient experience and function is considerable [10, 13].

In Australia, there are no specific MBS items for implantation of a phrenic nerve pacing

system. Possible item codes for surgery include dual chamber permanent trans venous

electrodes (MBS item 38356 [$837.35]) and anaesthesia, (20540 [$261.50]). Operating

theatre costs and in‐patient admission to intensive care would need to be accounted for.

Unable to obtain any information about whether phrenic nerve pacing would be funded by

a compensation scheme. Because are isn’t an MBS item for the procedure it would likely

need to be a special request.

Comparative respiratory treatment options

Various types of ventilation exist to assist patients who have difficulty breathing

independently. They can be invasive or non‐invasive, and can be further categorised into

positive or negative pressure ventilation. 1) Positive pressure ventilation: pushes air into the

lungs, 2) negative pressure ventilation: sucks the air into the lungs by making the chest

expand and contract. Negative pressure ventilators are rarely in use.

6.1 Position pressure ventilation

6.1.1 Invasive ventilation (also known as mechanical ventilation)

Invasive ventilation is and has been the standard treatment for respiratory device

dependent spinal cord injury patients. Air is forced into the lungs to enable lung function,

however, mechanical ventilation can impair the ability to cough and can limit speech [16].

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Comorbidity can include respiratory infections due to an impaired ability to cough. Regular

suction of secretions helps to avoid these complications, but is itself a potentially intrusive

and disruptive process for patients [16].

 Endotracheal intubation: the tube is inserted into the patient’s airway (trachea)

through the mouth or nose.

 Tracheostomy: is a tube inserted below the larynx to enable a patient to breathe

when there is an obstruction above the larynx.

6.1.2 Non‐invasive ventilation

Non‐invasive alternatives to mechanical ventilation, which may be used in some patients to

provide periods of time off mechanical ventilation Non‐invasive mechanical ventilators

come with masks and can be used at home. The two kinds are [17, 18]:

 Continuous positive airway pressure (CPAP): CPAP treatment uses a positive air

pressure to hold the airway open during sleep. The positive air pressure is generated

by a pump called a CPAP machine, and is applied through a small mask which fits

over the nose, or the nose and mouth and delivers constant and steady air pressure.

‐Auto‐titrating (adjustable) positive airway pressure (APAP): occurs in a

continuous positive airway pressure (CPAP) machine when the machine’s

sensor and internal algorithm adjust air pressure on a breath by breath basis.

 Bi‐level positive airway pressure (BiPAP): BiPAP is an adaptation of CPAP and delivers

two levels of positive airway pressure, an inhale pressure and an exhale pressure.

6.2 Negative pressure ventilators

During negative pressure ventilation, the airway opening is free, unlike in positive pressure

ventilation, and consequently, performing bronchial aspiration or bronchoscopy to remove

excessive airway secretions is easy. The major advantage of negative pressure ventilation is

the avoidance of invasive endotracheal intubation and its related complications. However,

limitations include lack of upper airway protection, possibility of obstruction in unconscious

patients and neurologic disorders, and many patients are restricted to the supine position

[19].

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 Portalung/Tank ventilator: is a rigid chamber in which the body of the person is

subjected to phasic negative and neutral pressure changes in order to cause lung

inflation and deflation. The person’s head is excluded from the chamber. (This

technique of artificial ventilation was formerly used in the treatment of victims of

poliomyelitis and was commonly known as an “iron lung” – because the chamber

was constructed of metal).

 Jacket Ventilator (Pulmo‐Wrap, Poncho‐Wrap): This ventilator is a windproof, water‐

permeable nylon parka suspended over a rigid grid that includes the rib cage and

abdomen. It allows the application of negative pressure over the anterior portion of

the chest wall. Airtight seals around the neck, arms, and hips are required to prevent

air leakage.

 Cuirass: This consists of a rigid shell fitting firmly over the anterior portion of the

chest. It applies negative pressure over a smaller surface area than either the iron

lung or jacket and is the least efficient NPV. Its efficiency improves if the anterior

abdominal wall is enclosed in the device and movement of the lateral aspect of the

upper rib cage is not restrained.

6.3 Additional respiratory supports

Air humidifier – is a machine that increases the humidity (moisture) in the air and is

commonly used to maintain respiratory comfort.

Portable suction machine (i.e. aspirator) – suction machines are used to remove unwanted

fluids such as saliva, mucus or blood, from a person’s airway to facilitate breathing.

Cough assist machine – is a device that mimics an effective cough. The machine pushes a

deep breath in the person’s lungs and then rapidly pulls that breathe out, mimicking a

cough, to ensure removal of airway secretions.

Oxygen concentrator – is a floor standing, electronically driven device that draws in air

through a fine filter. It removes nitrogen and allows only oxygen to pass through the outlet

Oxygen cylinders – portable oxygen cylinders are used when the patient leaves the home.

Used if there is a power failure.

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FOI 24/25-0889

7. Reference List

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Food and Drug Administration. Diaphragmatic Pacemaker Phrenic Nerve Stimulator. FDA Premarket Approval. Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P86002
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National Institute for Health and Care Excellence. Intramuscular diaphragm stimulation for ventilator dependent chronic respiratory failure caused by high spinal cord injuries. (2017). Retrieved from https://www.nice.org.uk/guidance/ipg594; Accessed: June, 2020.
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Velazco JF, Ghamande S, Surani S. Phrenic Nerve Pacing: Current Concepts. Current Issues and Recent Advances in Pacemaker Therapy. 2012 Aug 17:269.
NHS Commissioning Board Clinical Reference Group. Clinical Commissioning Policy: Phrenic Nerve Pacing Following Spinal Cord Injury. (2013). Accessed June, 2020. Retrieved from https://www.england.nhs.uk/wp‐content/uploads/2013/04/d13‐p‐ a.pdf
DiMarco AF. Phrenic nerve stimulation in patients with spinal cord injury. Respiratory physiology & neurobiology. 2009 Nov 30;169(2):200‐9.
Sieg EP, Payne RA, Hazard S, Rizk E. Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation?. Child’s Nervous System. 2016 Jun 1;32(6):1033‐8.

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Hirschfeld S, Exner G, Luukkaala T, Baer GA. Mechanical ventilation or phrenic nerve stimulation for treatment of spinal cord injury‐induced respiratory insufficiency. Spinal Cord. 2008 Nov;46(11):738‐42.
Le Pimpec‐Barthes F, Gonzalez‐Bermejo J, Hubsch JP, Duguet A, Morélot‐Panzini C, Riquet M, Similowski T. Intrathoracic phrenic pacing: a 10‐year experience in France. The Journal of thoracic and cardiovascular surgery. 2011 Aug 1;142(2):378‐83.
Khong P, Lazzaro A, Mobbs R. Phrenic nerve stimulation: the Australian experience. Journal of Clinical Neuroscience. 2010 Feb 1;17(2):205‐8.
Burns KE, Adhikari NK, Keenan SP, Meade M. Use of non‐invasive ventilation to wean critically ill adults off invasive ventilation: meta‐analysis and systematic review. Bmj. 2009 May 21;338:b1574.
Keenan SP, Sinuff T, Burns KE, Muscedere J, Kutsogiannis J, Mehta S, et al. Clinical practice guidelines for the use of noninvasive positive‐pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. Cmaj. 2011;183(3):14.
Moritz F, Brousse B, Gellée B, Chajara A, L’Her E, Hellot MF, Bénichou J. Continuous positive airway pressure versus bilevel noninvasive ventilation in acute cardiogenic pulmonary edema: a randomized multicenter trial. Annals of emergency medicine. 2007 Dec 1;50(6):666‐75.
Corrado, Antonio, and Massimo Gorini. “Chapter 16. Negative‐Pressure Ventilation.” Principles and Practice of Mechanical Ventilation, 3e Ed. Martin J. Tobin. McGraw‐Hill, 2013, https://accessmedicine.mhmedical.com/content.aspx?bookid=520&sectionid=

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