73 Acute pain in the intensive cardiac care unit

Pain is defined as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’ [1]. Historically, pain was regarded merely as a signal, warning of danger and prompting protective responses. However, its physiological, psychological, and ethical impact is significant, influencing disease course and patient journey. Individuals admitted to intensive cardiac care units (ICCUs) are at high risk of experiencing pain from their presenting pathology. Patient management must identify and treat pain, minimizing impact on patient outcomes.

The prevalence of pain (including procedure-associated pain) in general intensive care unit (ICUs) is estimated at 50% [2–5]. ICCU patients encompass both medical and surgical pathologies. However, post-cardiac surgery pain is most researched, with over 75% of patients recalling pain in the ICCU (60% rating the intensity as moderate/severe [6]). Thus, pain represents an unmet clinical need.

Pain is a common presentation of the ACS spectrum [7, 8], continuing until the cause of ischaemia is managed. However, research into pain intensity and duration in this population is lacking. Only recently has research considered pain as an integral symptom of other common medical cardiac conditions (e.g. cardiac failure). Sixty per cent of patients admitted to hospital with acute cardiac failure experience pain [9], with the pain intensity increasing relative to deteriorating cardiac function [10] (measured by EF and increasing NYHA classification).

Pain may arise from all tissues (see Table 73.1):

Understanding the physiological basis of each can help identify causes and aid in targeted management.

Pain is both a sensory and an emotional experience [1]. Perceiving noxious stimuli as pain involves integrating peripheral and central nervous system events (see Figure 73.1). This typically occurs as four distinct processes [11]:

The noxious stimulus is first converted into an electrical signal, i.e. an action potential (AP). This occurs at peripheral projections of primary sensory neurons, with free nerve endings lying within the tissue and sensitive to a number of physical and chemical stimuli. Activation occurs directly via ion channels on nerve endings, or through indirect pathways. Stimulus-specific ion channels include: thermally sensitive transient receptor potential (TRP) channels, proton-sensitive acid-sensing ion channels (ASICs), adenosine triphosphate (ATP)-sensitive purinergic ion channels (PTX), and K⁺, Ca²⁺, and Na⁺ voltage-gated ion channels. Channel activation alters the cation flow across neuronal membranes, causing localized depolarization and the production of an AP. Indirect pathways are a consequence of tissue injury, inflammation, and ischaemia. Cell damage, inflammatory cell migration, and mediator release activate nociceptors, directly (via ligand-gated ion channels) and indirectly (through metabotropic receptors), generating APs. Inflammatory mediators (e.g. cytokines) further sensitize nociceptors to subsequent stimuli.

APs are transmitted via the dorsal root ganglion (the location of nociceptor cell bodies) to the dorsal horn of the spinal cord. The majority terminate in superficial laminae (I and II). A smaller proportion project to lamina V. Second-order projection neurons transmit information to higher centres or act as interneurons, modulating transmission at the spinal cord level via a range of neurotransmitters (predominantly amino acids and peptides). Glutamate and aspartate act as major excitatory transmitters, through α-amino-3hydroxy-5methyl-4isaxazole propionic acid (AMPA), N-methyl-D-aspartate (NMDA), and metabotropic glutamate (mGluR) receptors.

A number of pathways transmit nociceptive stimuli to higher centres:

Additional connections to higher centres include:

Modulation of responses at the spinal cord level occurs via:

The balance between the peripheral nociceptive input, intrinsic spinal cord activity, and descending pathways from the brainstem determines the pain experience. This produces variable, individual responses to nociceptive stimuli.

Effective pain management starts with understanding the cause of pain; its nature and radiation patterns provide important clues. Knowledge of all the contributing causes guides management and individualizes effective treatment.

Pain is the most common symptom in patients presenting with MI (see Chapters 43 and 46) [7]. Most localize it (heavy or pressure-like) to the chest, but widespread radiation to the arms, back, neck, jaw, and abdomen occurs, as do atypical distributions (especially in the elderly). Although its mechanism is unclear, evidence supports an imbalance of O₂ delivery, causing a build-up of ATP, H⁺, bradykinin, K⁺, adenosine, and transient products of lipid oxidation [12]. These, and inflammatory mediators released upon plaques rupture, directly stimulate nociceptors and sensitize the surrounding nociceptors [13]. Pain continues, until anti-ischaemic interventions restore O₂ delivery, the effect of which can take several hours. Consequently, patients may require analgesia for hours, following definitive intervention [14].

Pain associated with heart failure is common [15], and the intensity increases with worsening cardiac function [9]. The location of pain is variable, occurring at multiple sites [16], less commonly in the chest [17]. Cardiac ischaemic pain is rare, despite being the commonest cause of failure. However, impaired organ and limb perfusion and capillary congestion produce mixed visceral and ischaemic pain. Complications of heart failure cause musculoskeletal pain (lack of physical conditioning) and skin breakdown.

Pain is a symptom of several inflammatory and infectious conditions, and analgesia is essential. The diagnostic criteria for pericarditis include an ischaemia-like retrosternal chest pain (CP) [18] and myalgia (see Chapter 58) [19]. Myocarditis and perimyocarditis also mimic ischaemia. Although CP is not typical in infective endocarditis (see Chapter 59) [20], non-specific back and joint pain is. Moreover, septic emboli may be painful.

Severe, abrupt ripping pain is the commonest presenting symptom of acute aortic dissection (see Chapter 61) [21, 22]. Thoracic aorta involvement can mimic MI. The pain location may reflect the site of intimal disruption, sometimes moving with extension [23]. Stretch and distension activate nociceptors in the aortic adventitia and nervi vascularis, with signals transmitted to the spinal cord via the aortic plexus and sympathetic ganglia [24]. Decreased coronary perfusion through changes in aortic distensibility causes ischaemic pain.

Pain from cardiac surgery (see Chapters 48 and 54) is multifactorial, with some elements common to all patients, and others being surgery-specific.

Somatic pain results from skin incisions, drains, and vascular cannulation sites, all of which induce inflammation (see Table 73.2 for common sites). Intraoperative tissue retraction, dissection, fractures/dislocations, and joint strain (sternoclavicular, acromioclavicular, and costovertebral) all cause inflammation and pain. Over time, the pain location changes [25]. Initially, pain originating from the surgical wounds and drains (both the drain site itself and referred pain commonly to the shoulder tip) predominates. However, generalized back, shoulder, and leg pain become more prominent features later. Where internal mammary artery conduits are used, patients experience greater pain [26–28]. Sadly, chronic pain, following surgery, occurs in up to 50%.

Visceral pain in surgical patients originates from pericardial, pleural, and diaphragmatic manipulation. Irritation from indwelling drains compounds matters. This contributes significantly to patient experience [29].

Neuropathic pain can occur acutely, following nerve damage, and may arise during:

Pain following transcatheter aortic valve implantation (TAVI) (see Chapter 59) common [30], but intensity is dependent on the approach:

Patients receive local anaesthetic prior to cardiac device placement (see Chapter 55). Inflammation from pouch dissection causes somatic pain in relevant dermatomes post-implantation. Pain duration and intensity, once the local anaesthetic effects diminish, is unclear; however, it is likely to be greater than stated in patient information literature. The commonest reason patients contact their general practitioners, following a device insertion, is pain.

Local anaesthetic infiltration is used prior to vessel cannulation for percutaneous coronary interventions. However, evidence suggests that over a third of patients continue to experience pain in the week following the procedure. Radial cannulation is associated with increased pain, compared with femoral cannulation, although pain from all sites appears to reduce over time [32, 33].

Patients may have other painful conditions (e.g. diabetes, arthritis) or chronic pain states (e.g. back pain, chronic cystitis, neuropathies). Discontinuing analgesia on admission, due to incomplete drug histories, limitations in delivery routes, or concern regarding potential adverse effects, can cause rebound and severe pain states.

ETTs (see Chapter 28) are a source of pain (reported as severe in 70% of patients [34]), as are vascular lines, catheters, drains, and face masks.

Procedures, including turning and mobilization, increase pain [4, 5], chest drain removal, arterial line insertion, and endotracheal suctioning being particularly painful [35]. Patients rarely receive analgesia [36], since staff regard these effects as transient. Unfortunately, when performed numerous times, they may cause central sensitization and chronic pain states. Patients admitted with medical diagnoses less frequently receive analgesia than surgical patients undergoing similar procedures [36].

Immobility, from sedation or following interventional procedures (e.g. angiography), causes pain. Physiotherapy (see Chapter 33), commonly used to minimize the consequences of immobility, is also painful [37]. Cardiac surgical patients experience more pain during recovery-essential activity (e.g. coughing, moving, deep breathing), compared to when at rest for days post-operatively [38].

Physiological, psychological, and ethical consequences of pain create a significant burden on patients, influencing both the disease course and patient journey.

The stress response, an integrated haemodynamic, metabolic, and immunological reaction, allows adaptation to insults (see Chapter 14) [39]. Triggers include trauma, critical illness, or inflammation [40]. Neuroanatomical overlap between the nociceptive and autonomic centres [41] and studies into post-operative analgesia [42–44] support theories that pain exacerbates this response [45, 46]. Whilst the stress response has protective effects, detrimental consequences occur and may influence outcome. The increased heart rate, inotropy, and blood pressure [47] result in increased cardiac work. The risk of arrhythmias increases, and hypercoagulation risks coronary/graft stenosis [48]. Infection and healing are altered, as pain impairs glucose tolerance and immunological function.

Cardiac patients are predisposed to decreased pulmonary compliance, premature airway closure, and V/Q mismatch secondary to low cardiac output (see Chapter 15). Pain exacerbates respiratory complications (e.g. atelectasis, infection) in spontaneously ventilating patients, due to guarding, restricted voluntary movement, impaired cough, and patients refusing physiotherapy. Reduced post-operative pain scores correlate with improved outcomes [49–51]. Adequate analgesia aids weaning of ventilated patients, with pain assessment reducing ventilator days [52].

Effective analgesia increases subcutaneous O₂ partial pressure [53]. This correlates with wound infection rates [54]; therefore, analgesia may contribute to wound healing—even in ‘day stay’ procedures (e.g. permanent pacemaker). Prolonged acute pain, following surgery, is a risk factor for developing chronic pain [55, 56]. This has physical, psychological, and social effects [57], impacting the quality of life [58]. Mechanisms behind chronic pain involve changes to the peripheral nerves, spinal cord, and higher central pain pathways [59].

Pain may cause short-term stress or long-term psychological illness (see Chapter 74). Critical care patients, relatives, and nursing staff identify pain as the most stressful experience during admission [60] and following discharge [61]. Anxiety before cardiac surgery is common [62] and associated with increased morbidity and mortality [63, 64]. Pain on discharge predicts the presence of anxiety and depression [65]. In heart failure, pain negatively affects the quality of life [10] and can lead to nightmares, sleeplessness, and feelings of helplessness.

All patients, including the critically ill, have the right to comfort (see Chapter 13) [66]. Failing to achieve this should be seen as a breach of human rights [67], and against the Hippocratic oath and the Declaration of Geneva. Inadequate pain relief (causing increased complications, time ventilated/in-hospital stay) flies in the face of the principle of distributive justice [68]. Moreover, negligence, and national constitutional and international human rights laws [67, 69] suggest that patients have a legal right to effective analgesia.

Pain assessments are conducted infrequently, are poorly documented by clinicians, and are performed using a range of assessment tools [70, 71]. Regular systematic approaches to assessment are known to improve outcomes.

The subjective, individual nature of pain makes it difficult to assess. However, assessment is fundamental to pain management, fulfilling two functions:

Simply assessing pain lowers the pain incidence and severity, reduces sedative requirements, decreases the duration of mechanical ventilation, and shortens the length of stay [52, 72]. This likely results from an increased vigilance of caregivers, prompting more appropriate pain management.

Variability in the assessment performance reflects the difficulty inherent in evaluating this complex experience. Pain lacks a linear relationship between ‘injury’ and individual experience. Therefore, patient self-reporting is accepted as the ‘gold standard’ assessment [73], removing inaccuracy and clinician bias [74, 75].

Reporting tools may be:

Unfortunately, some ICCU patients cannot self-report their pain. In these circumstances, a valid, reliable, structured tool is necessary. Historically, clinicians used physiological variables. Sadly, these are unreliable and inconsistent [73, 82], especially where sympathetic responses (tachycardia/hypertension) are altered by pharmacological interventions. A number of objective strategies utilizing physiological changes have been developed, including monitoring alterations in the autonomic nervous system and use of composite algorithms. However, none are currently validated to detect pain in the clinical setting [83]

Several behavioural tools exist to evaluate features, including expression, limb movement, lung compliance, and vocalization. The Behavioural Pain Scale (BPS) [84] or the Critical Care Pain Observation Tool (CPOT) [85] are recommended [73], as both are valid and reliable in patients with an intact motor function and observable behaviours [68]. They demonstrate good inter-rater reliability, and discriminative and criterion validity, in both French and English languages.

Both static (at rest) and dynamic (on movement) pain should be evaluated to avoid complications [37]. The frequency of assessment must be individualized, based on the severity, needs, and management [66]. Care bundle recommendations suggest at least four assessments in each shift [73], and reassessment after treatment is implemented. Trends provide useful information regarding the treatment effect, predicting events requiring analgesia and highlighting new pain.

Pain caused by certain cardiac conditions (e.g. ACS) only resolves, once definitive treatment for the medical condition becomes effective. However, pain resolution may have a time lag of hours, mandating interim analgesia. Other causes of pain require analgesia, irrespective of the disease course. Understanding the analgesic options, treatment effectiveness, and specific contraindications is essential.

Step one is realistic goal setting for patients, deciding what pain intensity is acceptable and achievable. This should guide analgesic plans. Communication with patients, and all those involved in their care, ensures consistent delivery [66]. Achieving optimal comfort often requires a number of interventions. The ICCU lends itself to implementing this in a protocolized, target-based fashion. A holistic multimodal approach, encompassing pharmacotherapy, and psychological, physical, social, and complementary interventions, enables all contributory factors to be addressed.

The timing of interventions is crucial to patient comfort. A pre-emptive approach, (predicting exacerbating events), rather than implementing strategies as a reaction to pain, is appropriate. In the ICCU, this is illustrated by the benefits of analgesia prior to drain removal [86, 87].

Choosing pharmacological analgesic agents in the ICCU is challenging. Patients have high incidences of altered physiology and organ dysfunction. Large interpatient pharmacokinetic and pharmacodynamic variability causes problems in predicting drug response. Routes of administration, drug distribution, metabolism, and excretion are all altered, as are the number and location of receptor populations. These may cause unpredictable analgesia and side effect profiles. Furthermore, analgesic recommendations, based on pharmacological safety data extrapolated from other patient groups, may not represent the true action in ICCU patients [88].

Opioids are the mainstay of ICCU analgesia [89]. They interact with central and peripheral opioid receptors (particularly mu and kappa). These inhibit the release of, and response to, neurotransmitters and thus nociceptive signal conduction. No alternative drugs display similar analgesic efficacy in moderate/severe nociceptive pain. Additional benefits include reduction in the affective components of pain and increased vagal tone (with venodilation and decreased heart rate). Commonly used opioids include morphine, fentanyl, and remifentanil. When titrated IV, all exhibit similar efficacies [73]. Other potential routes include enteral and transdermal, but absorption may be unpredictable in the critically ill. Agent choice should be governed by patient comorbidities and pharmacokinetic/pharmacodynamic properties of each drug. Following cardiac surgery, opioid patient-controlled administration devices provide better analgesia than nurse-controlled administration, probably due to increased consumption [90]. Additionally, opioid use can aid mobilization and discharge, following less invasive procedures such as device insertion.

Traditionally, caution regarding opioid prescribing occurred, due to side effects. However, they are usually dose-related and reduced by titrating the dose or switching opioids. Morphine analgesia is a class I recommendation for the management of ST segment elevation myocardial infarction (STEMI) [14]. However, the CRUSADE study [91] demonstrated that unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) patients who received morphine had an increased mortality rate. There were problems with selection bias and randomization, but further trials are clearly required. In the interim, the use of morphine for UA/NSTEMI patients has downgraded to class 2a evidence [8].

Multimodal analgesia is important in acute pain management and uses a number of synergistic drugs to facilitate opioid sparing.

Acetaminophen (paracetamol), administered enterally or intravenous (IV), is the foundation of any multimodal strategy. Commonly used to manage mild/moderate pain [92], it demonstrates significant morphine-sparing effects [93, 94], unfortunately without decreasing side effects [89]. Little ICCU evaluation has occurred, but side effects are mild (e.g. transiently abnormal liver function) [96].

Non steroidal anti inflammatory drugs (NSAIDs) use remains controversial. Acting via the inhibition of COX-1, COX-2, or both, they confer analgesic benefit to patients with mild/moderate pain. However, serious side effects can occur (GI bleeding, platelet inhibition, renal insufficiency). NSAIDs should be avoided in both UA/NSTEMI [8] and STEMI [14] patients where there is increased risk of death, reinfarction, and cardiac failure [97]. Furthermore, they precipitate heart failure in susceptible individuals and increase hospitalization rates [98, 99].

Patients who may benefit from NSAIDs are:

Gabapentinoids (gabapentin/pregabalin) reduce the hyper-excitability of dorsal horn neurons, in response to tissue injury, and are commonplace in neuropathic pain management. Their use, following cardiac surgery, decreases pain scores, opioid consumption, and pain at 3 months [101–103]. Their side effect profile is good, and they are recommended for ICU patients [73].

α2-agonists (e.g. clonidine, dexmedetomidine) have sedative, analgesic, and sympathomimetic actions. Their analgesic mechanism is controversial but may involve modulation in the dorsal horn and supraspinal regions [104]. They are opioid sparing [99] and reduce myocardial ischaemia [106]. Emerging trials in the ICCU suggest reduced rates of post-operative delirium and 1-year mortality [1071].

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, used as an adjuvant in post-operative pain [108, 109]. Evidence supporting its ICCU use is limited, but opioid sparing and improved patient satisfaction have been observed [110]. Concerns include the potential for distressing dreams and sympathomimetic effects.

Regional analgesia techniques are common in general, multimodal, and post-operative analgesia. Their use in the ICCU has been confined to patients following cardiac surgery and is controversial.

Thoracic epidurals (TEA) have received most attention. Meta-analyses conclude TEA patients have a lower incidence of complications (including renal failure, perioperative myocardial infarction, and arrhythmias) and reduced mechanical ventilation time and mortality [111, 112]. Despite these potential benefits, their use is not widespread. This reflects concerns regarding the risk of epidural haematoma (estimated at 1 in 3500) [112]. Currently, TEA is not recommended by the European Society of Anaesthesiology in this population [113]. However, the TAVI population may show benefits [114].

Further regional analgesia techniques include wound infiltration (single dose or catheter infusion), paravertebral, and intercostal blocks. However, minimal data support its effectiveness in cardiac populations.

Complementary analgesic techniques are low cost, simple to implement, and provide part of a caring patient environment. Most have lower (if any) side effect profiles. They are inadequate alone for anything other than mild pain; however, they may reduce analgesic requirements and improve patient experience:

Addressing these ‘softer’ issues can confer more sizable benefits than predicted.

The use of strong analgesic medications is hindered by patient and staff misconceptions (including fear of addiction and associations with palliative care). Staff education in pain leads to improved detection and management [127], especially when combined with standardized assessment tools and management protocols [5, 128].

Chronic pain, ‘pain without apparent biological value that has persisted beyond normal tissue healing time’ (usually taken to be 3 months) is common [123]. The incidence is estimated at around 20% [130, 131]. Although comprehensive knowledge of treatment regimens is limited, patients likely take multiple analgesics, with a large proportion on long-term opioid therapy.

Chronic pain patients have a ‘sensitized’ pain system. Physiologically, the nociceptive thresholds of spinal sensory neurons are lowered (central sensitization and endogenous opioid depletion). Patients risk heightened responses to painful stimuli and rebound chronic pain when analgesia is altered. It is important to understand what level of pain a patient experiences in the community (some are never entirely comfortable). This helps to plan realistic treatment goals during an ICCU admission. Individuals deserve honest conversations about achievable levels of analgesia.

Managing acute pain in chronic pain sufferers is difficult. Most important is appreciating that the presence of acute pain does not reduce the continued experience of chronic pain. This long-standing pain exists as a background or baseline pain, upon which acute pain occurs. Analgesia must cover that used in the community, with additional analgesia addressing the new acute pain. If possible, patients should continue normal medications by the normal route (as for non-analgesic agents). Unfortunately, pharmacokinetics of oral and transdermal medications can be affected by illness (e.g. reduced absorption in patients with gastroparesis or altered skin blood flow). Furthermore, in an attempt to simplify prescriptions in the ICCU, multimodal analgesia may be stopped, without instituting adequate alternatives.

The aims of management [132] should be to:

Staff require education; patients are not drug-seeking in the traditional sense and should be treated like any patient requiring analgesia. The consumption of morphine has increased recently, in part consequent upon opioid use in chronic non-cancer pain [134]. These individuals show tolerance to opioids, requiring substantially higher total daily and incremental doses of opioids than opioid-naive patients [135].

Tolerance can be addressed by two methods:

Stopping opioids in the acute setting may cause withdrawal symptoms (possibly occurring after only 2 weeks’ therapy), putting additional stress on a fragile cardiovascular system. Symptoms of sympathetic overactivity (anxiety, agitation, abdominal pain, and hallucinations) can be difficult to identify in the ICCU. However, staff should be aware of their presence and treat accordingly. Withdrawal also occurs when changing from long- to short-acting opioids. Short-acting opioid plasma concentrations dip frequently to levels precipitating withdrawal. In these circumstances, patients require either delayed-release preparations or infusions.

Chronic pain following sternotomy is common (incidence of 21–56%) [50, 137–140], and saphenous vein harvesting can cause saphenous neuralgia [141]. Both conditions arise from tissue destruction and nerve damage, causing neuropathic pain, which responds best to gabapentinoids or diclofenac. Alternative management strategies include lidocaine patches, tramadol, or regional interventions. Risk factors for developing chronic pain include non-elective surgery, resternotomy, and elevated post-operative pain scores [55]. This highlights the importance of managing pain in the ICCU to reduce the occurrence of chronic, debilitating conditions.

Chronic refractory angina is ‘characterized by the presence of angina caused by coronary insufficiency in the presence of coronary artery disease uncontrolled by conventional means’ [142]. It is thought this neuropathic syndrome occurs from a chronic increase in sympathetic tone, causing a vicious cycle of myocardial O₂ imbalance and myocardial dystrophy. This debilitating condition causes repeated hospital admissions, some to the ICCU. Multiple management strategies have been utilized [142].