Patient deterioration and advanced life support medicines

Case Scenario

The medical emergency team (MET) is called to review a 65-year-old man on the surgical ward. He is at day 4 following a Whipple’s procedure for pancreatic cancer. On arrival, he is noted to be hypotensive with a systolic blood pressure of 85 mmHg, bradycardic with a heart rate of 48 bpm, and hypoxic to 93% O2 on room air. The MET team initiates oxygen therapy, intravenous fluid bolus, and begin to investigate a cause for the deterioration. 

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Introduction

It is an Australian healthcare standard that all Australian hospitals have processes to identify, respond to and manage patients with an acute clinical deterioration, with the goal of reducing in-hospital cardiac arrest and mortality.^1,2 These processes include frequent monitoring and documentation of regular physiological observations, and guidelines around when and how to escalate care.¹ The use of medical emergency teams (METs), also known as rapid response teams (RRTs), is recommended by the Australian Resuscitation Council (ARC) to respond to instances of acute patient deterioration.¹ The composition of these emergency teams varies between hospitals, but frequently consists of nursing and medical staff with experience in critical care, with some sites internationally also including pharmacists in these teams.¹

Development of and evidence for medical emergency teams 

Patients often show some signs of physiological deterioration for several hours before cardiac arrest.³ Rapid response systems are designed to identify these patients and deliver interventions to alter the trajectory of deterioration.³

The implementation of these teams has demonstrated a reduction in mortality and cardiopulmonary arrests in both adult and paediatric populations.³

A statewide “Between the Flags” intervention rolled out in NSW in 2010 was designed to aid clinicians in the early detection of patient deterioration.⁴ This program has demonstrated a significant decline in intensive care unit and hospital mortality from cardiac arrest.⁴ Other states have implemented similar identification systems, including Q-ADDS (Queensland Adult Deterioration Detection System) and NEWS (National Early Warning Score).⁵

These identification systems are located on the observations chart and prompt nursing staff to initiate an urgent clinical review or MET call when observations such as heart rate, blood pressure, Glasgow Coma Score (GCS) or respiratory rate fall outside prescribed acceptable criteria. They also allow nursing staff to call for assistance if they are concerned about a patient who does not yet meet the prescribed call criteria.

Prior to the development of the MET call system, most hospitals had some version of a Code Blue team which responded primarily to patients in cardiac or respiratory arrest.⁶ These had a typical call rate of 0.5–5 calls per 1,000 hospital admissions, with a 70–90% in-hospital mortality.⁶ In comparison, the MET system has typical call rates of 20–40 calls per 1,000 hospital admissions, with a 0–20% in-hospital mortality.⁶

Causes of patient deterioration

Frequent causes of patient deterioration and MET activation include pulmonary oedema, sepsis, arrhythmias and seizures.⁷

A 2021 study conducted in two Victorian hospitals concluded that medicine-related events contributed to 23% of MET activations, with 63% of these potentially preventable.⁸ Medicines affecting the cardiovascular system contributed to 60% of the total.⁸ Tachycardia due to omission of beta- blocking medicines, and hypotension due to cumulative toxicity or inappropriate use of antihypertensives during acute illness, were the most common preventable medicine causes of MET calls.⁸ These MET activations tended to occur earlier in the hospital stay than MET activations for other causes, and these patients were more than 50% likely to require repeat MET activations.⁸

Another study which reviewed RRTs in a United States centre identified that 88% of calls were for impending respiratory failure due to excessive fluid administration in surgical patients.⁹

Cardiac arrest and advanced life support

If early signs of patient deterioration are not detected and timely intervention made, patients may progress to cardiac arrest. All hospital staff should be able to recognise cardiac arrest, call for help, start cardiopulmonary resuscitation (CPR) and defibrillate using an automated defibrillator. These steps are commonly referred to as basic life support (BLS).¹⁰

The purpose of BLS is to maintain myocardial and cerebral oxygenation until advanced life support (ALS) personnel and equipment are available.¹ Effective BLS may increase the likelihood of successful defibrillation and return of spontaneous circulation (ROSC).¹

The traditional ALS or Code Blue team composition is similar to the medical emergency team, often with the addition of a doctor trained in airway management.⁹

The role of the ALS team is to continue basic life support measures (CPR and defibrillation), with the additional roles of airway management, medicine administration, and identifying and treating potentially reversible causes of cardiac arrest.¹⁰

Treatable causes for cardiac arrest are referred to as the 4Hs and 4Ts¹¹:

• Hypoxaemia
• Hypovolaemia
• Hyper/hypokalaemia and metabolic disorders
• Hypo/hyperthermia
• Tension pneumothorax
• Tamponade
• Toxins/poisons/drugs
• Thrombosis – pulmonary/cardiac. 

Medicines for cardiac arrest

No medicine used during cardiac arrest has been demonstrated to improve long-term survival.¹² They are used because of their theoretical benefits, with some limited evidence for improvement in short-term survival rates.^12,13

The intravenous (IV) route is the preferred route for medicine administration during CPR. If IV access is not able to be obtained in a timely manner, intraosseous (IO) administration is the second-line route recommended by the ARC.¹² All medicines administered during CPR should be followed by a fluid flush of at least 20–30 mL. This reduces the time for the medicine to reach the central circulation. Lower limb veins are not recommended for medicine administration due to the lack of circulation below the diaphragm during cardiac arrest.¹² Obtaining IV access and administration of medicines should not interfere with ongoing good quality CPR.¹⁴

Adrenaline (epinephrine)

Adrenaline is the first-line medicine administered in all cardiac arrests.¹² It is a naturally occurring catecholamine which acts on alpha and beta adrenoreceptors. It is the alpha effects, resulting in vasoconstriction of peripheral blood vessels, and redistribution of the available circulatory output to the brain and myocardium which provides its theoretical benefits in this scenario.¹²

A standard dose of 1 mg for adult patients is administered either as soon as vascular access is obtained, if the arrest is due to a non-shockable rhythm, or after the second shock is administered, for shockable rhythms.

Further doses can be administered after every second loop of the resuscitation algorithm.¹² Adverse effects of adrenaline administration include tachyarrhythmias, severe hypertension after resuscitation and tissue necrosis if extravasation occurs.¹²

Amiodarone

Amiodarone is a class III antiarrhythmic medicine which works on sodium, potassium and calcium channels as well as having alpha and beta-adrenergic blocking properties.¹²

It is the preferred antiarrhythmic for cardiac arrests because of two randomised controlled trials (RCT) published in 2005. These trials compared amiodarone to lidocaine (lignocaine) for out-of-hospital cardiac arrests.

These trials demonstrated a survival to hospital admission advantage with amiodarone compared to lidocaine; however, they did not show a survival to hospital discharge improvement.¹⁴

A 300 mg dose is administered as a bolus injection for refractory VF (ventricular fibrillation)/pulseless VT (ventricular tachycardia) between the third and fourth shocks.¹² An additional 150 mg can be administered following the fifth shock.^10,12

A continuous infusion can be initiated following ROSC for prophylaxis of recurrent arrhythmias.¹² Cardiac arrest is the only indication for the bolus injection of amiodarone. All other indications should be given as an infusion.¹³ Adverse effects of amiodarone in the resuscitation setting include hypotension, bradycardia and heart block.¹²

The ARC guideline Medications in Adult Cardiac Arrest does not list any contraindications to the use of amiodarone in this setting, despite its complex pharmacokinetics, drug interactions and adverse effects.¹² Once ROSC has been obtained and the patient is stabilised, these issues can be addressed.

Lidocaine (lignocaine)

Lidocaine is a class IB antiarrhythmic medicine. It is now listed in the ARC guidelines as an alternative to amiodarone in patients with refractory VF/pulseless VT.¹²

The standard dose is 1 mg/kg (as a bolus injection) with an additional 0.5 mg/kg bolus if required.¹² Adverse effects of lidocaine in the resuscitation setting include hypotension, bradycardia and altered central nervous system.¹² A summary of key medicines used for cardiac arrest is provided in Table 1.

Table 1 – Medicines for cardiac arrest

References: ANZCOR¹², Symons K ed¹³

Electrolytes

In specific circumstances, electrolytes are administered as part of the management of a cardiac arrest (Table 2).

Table 2 – Electrolytes used in the management of cardiac arrest

References: ANZCOR¹², Symons K ed¹³

Thrombolysis

Routine use of thrombolytic medicines during cardiac arrest is not recommended due to unclear evidence of benefit and an increased rate of intracranial bleeding.¹²

They may be administered for cardiac arrest due to suspected or confirmed pulmonary embolism.¹² The ARC recommends CPR be continued for 60–90 minutes after administration of thrombolytic medicines before termination of resuscitation.

There is no specific guidance in the ARC guidelines regarding the use of these medicines in high-risk patients (such as recent intracerebral bleed or major surgery). In this situation, it would be the decision of the senior medical officer managing the arrest to determine the risk–benefit for the patient.

Pharmacists in METs and advanced life support

A small number of studies have demonstrated the benefits of pharmacist involvement in both MET and Code Blue teams. Roles include sourcing and dosing of medicines and ensuring compliance with guidelines.¹⁵

With up to a quarter of MET calls potentially caused by medicine errors,⁷ there is an obvious role for pharmacists here. Where pharmacists have been involved in RRTs, this has been well received by other team members.¹⁶

While pharmacists as members of the MET are yet to become ubiquitous in Australian hospitals, pharmacists have a role in the governance of medicine management for MET and ALS to ensure that essential medicines are available when required, and that members of the MET have access to guidelines and training to assist with medicine administration.⁶

There are currently no standard recommendations for which medicines should be available for medical emergency teams, and practice can vary widely between hospitals.⁶ Principles of MET medicine management to facilitate safe, timely and effective access to, selection of and administration of medicines have been proposed.⁶ These principles include:

• MET medicine management should be multidisciplinary, involving ward staff and MET nurses, doctors and pharmacists.
• Medicines should be available to the MET to manage the common causes of MET activation, but not duplicate other resources.
• Changes to medicine supplies should be based on the best available evidence, including feedback from ward and MET clinicians, data from local MET calls, interventions, and activation triggers, in addition to published literature and guidelines.

Pharmacists should be involved with these governance activities to ensure the MET can continue to provide timely interventions for deteriorating patients.

Knowledge to practice

Early recognition and prevention of patient deterioration is an important component of the healthcare system. Medicine usage contributes to this, both as a potential cause of deterioration, and for the treatment of deterioration when it occurs.

As the medicine experts in the healthcare team, pharmacists can provide support by reviewing patients when they deteriorate and assisting in identifying potential medicine causes for the deterioration. Pharmacists also play an essential role through the provision of clinical advice on medicine dosing, administration and IV compatibility, and ensuring the emergency team have the necessary medicines when they are required.

Pharmacists as members of the medical emergency team remains an emerging role. 

Conclusion

Early detection and treatment of deteriorating patients are crucial components of quality health care. Pharmacists have an important role in supporting the medical emergency team in providing this essential service. 

Key Points

• Medical emergency teams within hospitals respond to acute patient deterioration with the aim of preventing patient morbidity and mortality.
• Medicine errors may contribute to around a quarter of MET call activations.
• Advanced life support is a set of protocols that extend basic life support to further support circulation and airway management.
• No medicine used in advanced life support has evidence of improving long-term survival. Medicines are used to support ongoing cardiopulmonary resuscitation and defibrillation attempts.
• Pharmacists can contribute to the medical emergency team by providing clinical advice on medicine dosing, administration and IV compatibility, and ensuring medicines can be easily located in an emergency.

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References 

1. Australian and New Zealand Committee on Resuscitation. Guideline 11.1 – Introduction to and principles of in-hospital resuscitation. ANZCOR; 2019.
2. Australian Commission on Safety and Quality in Health Care. National consensus statement: essential elements for recognising and responding to acute physiological deterioration. Third edn. ACSQHC; 2021.
3. Maharaj R, Raffaele I, Wendon J. Rapid response systems: a systematic review and meta-analysis. Crit Care 2015;19(1):254.
4. Bhonagiri D, Lander H, Green M et al. Reduction of in-hospital cardiac arrest rates in intensive care-equipped New South Wales hospitals in association with implementation of Between the Flags rapid response system. Intern Med J 2021;51(3):375–84.
5. Campbell V, Conway R, Carey K et al. Predicting clinical deterioration with Q-ADDS compared to NEWS, Between the Flags and eCART track and trigger tools. Resuscitation 2020;153:28–34.
6. Jones D, DeVita M, Bellomo R. Rapid-response Teams. N Engl J Med 2011;365(2):139–46.
7. Levkovich B, Jones D, Bingham G, et al. Evaluation of medical emergency team medication management practices in acute hospitals: a multicentre study. Aust Crit Care 2022;35(1):59–65.
8. Levkovich B, Orosz J, Bingham G, et al. Medication-related medical emergency team activations: a case review study of frequency and preventability. BMJ Qual Saf 2022. Epub 2022 July 15. 
9. Kaplan LJ, Maerz LL, Schuster K, et al. Uncovering system errors using a rapid response team: cross-coverage caught in the crossfire. J Trauma 2009;67(1):173–8. 
10. Soar J, Bottiger BW, Carli P, et al. European Resuscitation Council Guidelines 2021: adult advanced life support. Resuscitation 2021;161:115–51.
11. Australian and New Zealand Committee on Resuscitation. Guideline 11.2 – Protocols for adult advanced life support. ANZCOR; 2018.
12. Australian and New Zealand Committee on Resuscitation. Guideline 11.5 – Medications in adult cardiac arrest. ANZCOR; 2016.
13. Symons K ed. The Australian injectable drugs handbook. 8th edn. Melbourne: Society of Hospital Pharmacists of Australia; 2020.
14. Eng Hock Ong M, Pellis T, Link M. The use of antiarrhythmic drugs for adult cardiac arrest: A systematic review. Resuscitation 2011;82:665–70.
15. Feih J, Peppard WJ, Katz M. Pharmacist involvement on a rapid response team. Am J Health-Syst Pharm 2017;74(Supp 1):S10–S16.
16. McGinnis C, Kim C, Scholle C, et al. Evaluation and perception of clinical pharmacist participation in a rapid response team during cardiopulmonary resuscitation. Q Manage Health Care 2022;31(1)34–7.

BELINDA BADMAN BPharm, GradDipClinPharm, AdvPP(II), MSHP is Senior Critical Care Pharmacist and Critical Care Team Leader at Princess Alexandra Hospital, Brisbane.