1

Introduction

Thoracic surgery is not without risk. The combination of surgical trauma and resection of vital functional tissue, often against a background of deconditioning, chronic obstructive pulmonary disease (COPD) and other comorbidities, means that surgery for lung cancer is associated with complications in up to 44% of cases [ ]. Adverse events lead to delayed recovery, poorer long-term outcomes, higher costs, and unplanned readmissions. Long-term survival is also reduced, and this effect is more pronounced for more serious complications [ ]. Quality of life and functional decline appear to be affected by the length of hospital stay rather than the complication itself [ ]. Unplanned readmission is not a benign event and results in worse outcomes, including a reduction in short- and long-term survival [ , ].

Perioperative care is often suboptimal, non-standardized and dogmatic. The principle focus of thoracic surgeons and anesthesiologists has historically been the few hours in the operating room with less attention paid to preoperative optimization or proactive postoperative care. In recognition of the adverse influence of non-evidence-based and non-standardized perioperative care, and following initial popularization in colorectal cancer surgery, enhanced recovery after surgery (ERAS) pathways have become widespread in all surgical specialties [ ]. In thoracic surgery, guidelines on perioperative care have been produced by the ERAS Society/European Society for Thoracic Surgery (ESTS) [ ], the French Society of Anesthesia and Intensive Care Medicine (SFAR)/French Society of Thoracic and Cardiovascular Surgery (SFCTCV) [ ], and the Italian intersociety consensus on Perioperative Anesthesia Care in Thoracic Surgery (PACTS) [ , ]. A systematic review and meta-analysis of ERAS in thoracic surgery has confirmed that adoption of ERAS pathways leads to a reduction in complications, length of stay and readmissions [ ].

In this review, those elements of care that are most important in the period following lung resection surgery are described in the context of the guidelines and more recent evidence and are summarized in Table 1 . Furthermore, the interplay between these elements is explored and there is a renewed focus on what can be achieved in the first 24 h after surgery.

2

Enhanced recovery after surgery

Lung cancer surgery is a traumatic surgical intervention. Not only is there damage to nerve, muscle and bone, but there is also the removal of functional lung tissue. As many of these patients have COPD, an already compromised respiratory state is compromised further. The extent of lung resection is also an important factor in determining the risk of postoperative morbidity and mortality and is central to all guidelines on determining a patient’s fitness for surgery.

In common with all other major surgeries, lung resection is associated with what can be a profound homeostatic disturbance often referred to as the surgical stress response. Following activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, a neuro-humoral reaction occurs characterized by a rise in circulating glucocorticoids, catecholamines and glucagon. It is mediated by afferent nerve impulses and cytokines released from the surgical site. The result is whole body catabolism, increased oxygen demand and hyperglycemia, the latter developing due to a multitude of factors including insulin resistance [ , ]. The consequences of these processes can be harmful. For example, catabolism is associated with loss of protein (e.g., from muscle) and cellular dysfunction, while insulin resistance is associated with impaired cellular function at the injury site [ ].

Many factors influence the degree of harm sustained by the patient in addition to their functional recovery and are summarized in Fig. 1 . An inadequate functional recovery will translate into a greater risk of postoperative morbidity and mortality and a longer length of stay [ ]. Following discharge, these patients are more likely to be readmitted to hospital or require ongoing care in the community [ ].

The deterioration and functional recovery of a patient during and after surgery is influenced by potentially modifiable factors. Black line: trajectory of a traditionally managed patient. Blue line: trajectory of a patient managed on an ERAS pathway. Dotted line: minimum level of functioning required to achieve independence.

BMI: body mass index. IV: intravenous. VATS: video-assisted thoracic surgery. RATS: robot-assisted thoracic surgery. VO ₂ max: maximal oxygen delivery.

ERAS pathways aim to mitigate the surgical stress response. The focus is shifted from the short time in the operating room to the entire patient pathway with an emphasis on the quality of a patient’s recovery [ ]. Multiple evidence-based interventions or care elements are introduced, covering the four key phases of a patient’s journey: pre-admission, admission, intraoperative and postoperative. At the same time, interventions that are dogmatic, unnecessary, or harmful (such as fasting, excessive opioids or enforced immobility) are removed from the pathway. Carbohydrate loading and optimal pain control can reduce insulin resistance. Preoperative nutritional support and early feeding after surgery can minimize the impact of catabolism, while regional anesthesia and effective analgesia can reduce the endocrine stress response. Throughout all of this, the maintenance of euvolemia prevents organ dysfunction by maintaining cardiac output and oxygen delivery. The net result is a quicker recovery from surgery, a more rapid restoration of normal function, and a reduction in complications.

Fast-track protocols have previously been described in thoracic surgery and appeared to show an improvement in patient outcomes. Now, specific ERAS pathways for lung cancer surgery have been published [ ] and consistently demonstrate improvements in complication rates, length of stay, readmission rates and costs. A meta-analysis has confirmed the benefits of ERAS pathways in this group of patients [ ]. There are also demonstrable benefits in other metrics following surgery, including opioid use in hospital and subsequently following discharge [ , ]. This has clear implications for the growing opioid epidemic seen in many countries [ ].

3

Atrial fibrillation prevention

Although new onset postoperative atrial fibrillation and flutter (POAF) is common after thoracic surgery, there is little evidence that POAF prophylaxis improves patient outcomes. Despite this, interest in chemoprophylaxis remains.

POAF has an incidence of around 12% following lung resection [ , ]. Contributory factors include increasing age, male sex, Caucasian race, hypertension, COPD, heart failure and valvular heart disease [ ]. A video-assisted thoracic surgery (VATS) approach is not protective against POAF following lobectomy. While this was initially thought to be the case, it is not a consistent finding [ ] and is certainly not demonstrated in the randomized controlled trials (RCTs) of VATS versus open lobectomy [ , ]. However, increasing the extent of lung resection (e.g. pneumonectomy compared to lobectomy) does appear to increase the risk [ ]. Of note, the incidence of POAF within thoracic ERAS programs is low [ ] suggesting that the reduced inflammatory response associated with ERAS may be protective.

The likelihood of POAF doubles in the presence of postoperative complications [ ]. POAF occurring in isolation is associated with an increased length of hospital stay and an increased risk of readmission. Importantly, patients experiencing POAF along with other complications do poorly and have an increased risk of stroke and in-hospital death. This is seen in all surgical specialties and has provided the basis for the recommendation to consider long term oral anticoagulants in those patients who develop POAF [ ].

Several prevention strategies have been recommended in the 2014 American Association for Thoracic Surgery (AATS) guidelines for the prevention and management of POAF following thoracic surgical procedures [ ].

• 1
  

  Beta-blockers

In non-cardiac surgery, initiation of beta-blockers perioperatively has previously been actively discouraged owing to an increased risk of death seen in one trial. A more recent meta-analysis has not confirmed this [ ]. Nevertheless, there does not appear to be a consistent role for de novo perioperative beta-blockers to prevent POAF.

Conversely, patients taking beta-blockers prior to surgery are at risk of developing POAF if they are withdrawn abruptly. As such, beta-blockers should be continued into the postoperative period without a break.

• 2
  

  Magnesium

In those patients who are magnesium deplete (either with a low serum magnesium or suspected total body magnesium depletion), the use of intravenous magnesium may be considered and can be given perioperatively. It is currently the focus of several RCTs. As magnesium is commonly used as an adjunct to pain relief in ERAS programs, it is likely to be given anyway.

• 3
  

  Digoxin

Digoxin does not prevent the development of POAF and should not be used.

• 4
  

  Diltiazem and Amiodarone

In patients deemed at particular risk of developing POAF, the 2014 AATS guidelines state that it is reasonable to consider perioperative diltiazem (assuming the patient is not taking beta-blockers and cardiac function is normal) or postoperative amiodarone. However, it should be noted that no clinical model has been developed to identify high-risk patients after lung resection, although the CHADS ₂ score may have some utility [ ].

In summary, while the administration of diltiazem preoperatively or amiodarone postoperatively may be reasonable in patients deemed at high risk, there is no validated system to identify these patients and, more importantly, there is little evidence that POAF prophylaxis improves outcomes.

4

Postoperative fluid and diet management

Patients should emerge from the operating room in a euvolemic state having been maintained on 2–6 ml/h of intravenous (IV) balanced crystalloid while avoiding overly restrictive or liberal fluid regimens [ ]. The ERAS Society/ESTS guidelines suggest early cessation of these IV fluid infusions with enteral fluid resumption as soon as the patient is lucid and able to swallow (normally within an hour of surgery) [ ]. The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend that oral intake should be continued after surgery without interruption, and the expectation is that oral fluids should be started almost immediately [ ]. There is evidence that this is associated with reduced complications and a shorter length of postoperative stay.

Little has been published about postoperative IV fluid infusions after thoracic surgery. One study showed that infusions of more than 1,410ml/24 h were associated with pulmonary complications, as were infusion rates of less than 1,080ml/24 h [ ]. However, it is difficult to know how to interpret these results as the intraoperative IV fluid infusion rates were high (around 12 ml/kg/hr) and oral fluids and diet were not resumed until 6–8 h after surgery. Therefore, it seems reasonable to stop IV fluid infusions as soon as the patient is drinking normally. This should be achievable within an hour or so of surgery [ ].

5

Early mobilization

After thoracic surgery, barriers to early mobilization include the presence of chest tubes, transurethral catheters and IV fluids. Pain, both surgical site and drain-related, is also a significant factor. Inadequate pain and postoperative nausea and vomiting (PONV) control disempowers and deters patients and limits their ability to mobilize.

Reduced mobility and activity results in physical deconditioning, diminished muscle mass and functional decline [ ]. This in turn leads to an increased risk of complications including atelectasis, pneumonia and VTE. This risk is magnified by the stress of surgery. Early mobilization is an intuitive component of ERAS and is meant to counteract the harmful effects of immobility.

Patient posture also affects lung function and oxygenation. In one prospective study following VATS lobectomy, supine, sitting and standing positions were adopted by patients in the days after surgery [ ]. Both FEV1 and oxygen saturations increased as the patients became more vertical (i.e., went from lying to standing) although this was not correlated to clinical outcomes.

So far, systematic reviews have failed to demonstrate the benefits of early mobilization on postoperative outcomes, mainly due to the poor quality of included studies and conflicting results [ , ]. Nevertheless, postoperative immobility is reported as a significant risk factor for ERAS deviation and prolonged length of stay following colorectal surgery [ ], and it is associated with increased morbidity and length of stay following lung cancer resection [ , ]. Several studies following major thoracic surgery have had impressive beneficial effects on pulmonary complications and length of stay by focusing on early and aggressive mobilization strategies, including ambulation within 1 h of surgery [ , ].

All the guidelines for thoracic perioperative care concur that patients should be mobilized as soon as possible, ideally on the day of surgery and certainly within the first 24 h, to avoid the deleterious effects of bed rest. The ongoing presence of a chest tube can deter patients from mobilizing and so should be removed as soon as possible. Other barriers to mobilization, such as inadequate pain and PONV control or the presence of transurethral catheters and IV fluids, can be mitigated using ERAS protocols.

6

Pain relief

A thoracotomy is one of the most painful incisions in surgery, while a VATS (or robotic) approach has smaller benefits than most minimally invasive surgeons believe when compared to open surgery [ , ]. Postoperative pain, whether secondary to open or minimally invasive surgery, is often severe and can be due to peripheral nerve damage, muscle injury, fractured ribs, or injury to the intercostal nerves. Intercostal nerve injury appears to be the most significant factor in its pathogenesis [ ]. Indwelling chest tubes may cause ongoing irritation of the pleura or intercostal bundles.

Analgesia within an ERAS pathway for thoracic surgery must combine multiple interventions. A standardized multimodal analgesic strategy should allow for early mobilization and reduce the risk of pulmonary complications. Although minimally invasive surgery does confer some benefit, other important interventions include patient education and early chest tube removal.

Pain relief pathways should include multimodal enteral and parenteral analgesia with regional anesthetic techniques while attempting to avoid opioids and their side effects. Short-term opioid prescriptions are often necessary immediately after thoracic surgery but have well-documented acute effects (nausea, constipation, sedation, depressed ventilation, and suppression of coughing) which may affect a patient’s ability to achieve ERAS targets such as PONV control, early mobilization, and a quick return to oral diet. In the longer-term, they may adversely affect cancer survival [ ].

Despite this, some ERAS programs have managed to achieve opioid-free discharges in the majority of their postoperative patients [ ].

The recommendations for regional anesthesia following lung cancer surgery suggest thoracic epidurals should be avoided to minimize side effects such as PONV, pruritus, hypotension, urinary retention [ , , ]. There is most evidence for paravertebral blockade, but erector spinae and serratus anterior planar blocks are relatively easy to place. Intercostal blocks tend to be adjuncts to these techniques. Systemic analgesia should include acetaminophen in combination with non-steroidal anti-inflammatory drugs when not contra-indicated [ , , ]. Glucocorticoids may be administered to prevent PONV and reduce pain although their efficacy is being questioned. Ketamine should also be considered, particularly in patients with pre-existing chronic pain [ , ]. Other potential adjuncts used in ERAS programs, such as dexmedetomidine, liposomal bupivacaine or the prophylactic use of gabapentinoids, are either unproven or are subject to ongoing studies.

The adoption of ERAS pathways has been shown to reduce the need for opioids both in-hospital [ , ] and following discharge [ , , ]. Furthermore, early removal of chest tubes and subsequent early omission of opioids are independently associated with better patient outcomes within an ERAS pathway [ ].

7

Chest tube management

Chest tubes are a ‘necessary evil’ following most cases of lung resection. They are required to expel air, blood and pleural fluid, enable lung re-expansion, and monitor for potential postoperative blood loss amongst other functions. However, they are painful and can limit mobility. Pain is both musculoskeletal and neuropathic in nature. ‘Drain pain’ can have several adverse effects.

• 1.
  

  Inadequate provision of analgesia may exacerbate an already compromised respiratory state and respiratory failure can occur due to painful splinting of the chest. Furthermore, an inadequate cough response can cause retained secretions and, ultimately, pneumonia.

  
  
• 2.
  

  Increased opioid requirements can cause gut stasis and constipation, PONV, sedation, and suppression of ventilation.

  
  
• 3.
  

  Pain and the side effects of opioid analgesia can also contribute to immobility.

Conservative chest tube management strategies contribute to these issues. The use of an underwater seal, particularly if routine wall suction is applied, contributes to immobility. Dogmatic thresholds regarding pleural fluid outputs can keep chest tubes in for days. The lack of digital drainage systems increases inter-observer variability in the assessment of the presence of a potential air leak, again contributing to inertia in chest tube removal. Chest tube management should therefore be approached in an evidence-based way and conservative removal strategies abandoned. This should facilitate early chest tube removal, which has been shown to result in better pain control and improved respiratory function [ ], and should lead to better PONV control, improved mobility, and better patient outcomes.

8

Which ERAS care elements are most important?

An editorial concerning the ERAS Society/ESTS guidelines has been critical of the number of care elements required to implement a full-blown ERAS program [ ]. The guidelines may indeed seem daunting as there are 45 individual recommendations. It was suggested that clinicians should concentrate on the key components for an early recovery instead of trying to implement all 45.

This argument does have merit. The philosophy of ERAS includes the concept that, while an individual care element by itself may not have a great impact, there is a synergistic beneficial effect on patient outcomes when combined with multiple other key care elements which themselves may have similarly small individual effects. This is the ‘aggregation of marginal gains’ approach popularized by elite sporting teams. The ‘key care elements’ approach, however, suggests that just a few care elements are vital while the others may be superfluous.

In 2 studies looking at the effect of ERAS compliance on outcomes after lung surgery, greater compliance with the overall ERAS pathway was shown to lead to better outcomes, supporting the ‘aggregation of marginal gains’ hypothesis for the success of ERAS programs. At the same time, however, some ‘key care elements’ were found to be independently associated with better outcomes: preoperative carbohydrate loading; a VATS approach; early mobilization; early chest tube removal; and early discontinuation of opioids [ , ]. It would seem, therefore, that implementing the whole pathway is ideal, but much can be gained by focusing on just a few important elements.

9

Interplay between postoperative ERAS care elements

Thoracic surgery is painful. Chest tubes cause additional pain and inhibit pulmonary function, irrespective of the surgical approach [ ]. Opioids are often given to manage both post-thoracotomy pain and ‘drain pain’ and can result in PONV, drowsiness and immobility. Immobility and its deleterious effects are often seen because of conservative chest tube management strategies and over-reliance on opioid analgesia. Furthermore, inadequate pain control despite opioids can exacerbate an already compromised respiratory state. The consequences of this have all too often been seen with some patients rapidly deteriorating due to respiratory failure secondary to splinting, ineffective cough, poor clearance of secretions and pneumonia.

It should be appreciated, therefore, that chest tube management is an integral and important part of ERAS pathways as many postoperative ERAS care elements are intertwined. A conservative approach to chest tubes adversely affects pain relief (and opioid management), PONV control, and the ability to mobilize. Proactive chest tube management is therefore crucial in optimizing outcomes, influencing both the speed of recovery and the length of hospital stay.

10

Day 0

The postoperative phase on the day of surgery, or day 0, is often the forgotten day in terms of proactive patient management and recovery. This is due to several factors including patient expectations, a lack of institutional day 0 protocols, a dogmatic adherence to bed or chair rest in the immediate surgical aftermath, and a lack of awareness of the evidence. It is at this point that the patient is at their nadir ( Fig. 1 ) and may benefit most from proactive intervention. In the context of effective analgesia and PONV relief, there should be a focus on early mobilization and potential removal of chest tubes, even after anatomical lung resection.

Several studies have shown the benefit of ultra-early mobilization within an hour of emergence from anesthesia. One focused on rehabilitation in the post-anesthesia care unit (PACU) [ ]. Physiotherapy with or without ambulation was commenced an hour after tracheal extubation. At the same time the IV line was locked. There was a demonstrable decrease in the incidence of postoperative atelectasis and pneumonia. Another study focused on aggressive ambulation both before and after VATS lobectomy [ ]. Patients were walked around the PACU within an hour of extubation before walking from the PACU to the ward. The results were impressive with very low rates of pneumonia and a median length of stay of only one day following surgery.

Chest tube management strategies on the day of surgery are generally conservative. Despite this there has been evidence for some time that a chest tube can be removed in the operating room or shortly afterwards for more minor procedures such as lung wedge resections or mediastinal surgery [ ]. One recent study has shown that the use of a digital drainage system allows the safe removal of a chest tube just 4 h after surgery in those patients undergoing VATS lobectomy or segmentectomy [ ]. 45% of chest tubes were removed on day 0 and no tube had to be re-inserted for pneumothorax. Furthermore, those patients who had early chest tube removal were more likely to be opioid-free by the first postoperative day and had a median length of stay of only one day.

11

Summary

Thoracic surgery usually involves a harmful surgical stress response in combination with the removal of lung tissue, often in patients who are already functionally compromised. Management of the postoperative period requires taking patients from their nadir at the end of their lung resection to a level at which they are functionally independent in just a few days. ERAS incorporates many evidence-based interventions which mitigate the effects of the surgical stress response with the explicit aim of hastening a return to normal function. Early mobilization, proactive chest tube strategies and opioid-sparing analgesia appear to be the most important postoperative goals of ERAS pathways. These ERAS care elements are all intertwined with one affecting the other. Other ERAS care elements, such as atrial fibrillation prevention and the early restoration of oral fluids and diet, are probably less important but should be seen as part of the introduction of multiple small synergistic interventions. Adopting ERAS can be challenging, but both the ‘aggregation of marginal gains’ and the ‘key care elements’ approaches result in improved outcomes. For patients, that means fewer complications, a shorter length of stay and a better overall recovery.

12

Practice points

• •
  

  The key postoperative ERAS care elements are early mobilization, early chest tube removal and early cessation of opioids

  
  
• •
  

  There is little evidence that atrial fibrillation prophylaxis improves outcomes

  
  
• •
  

  In patients taking beta-blockers, they should be continued through the perioperative period

  
  
• •
  

  Oral fluids should be started and IV fluid infusions stopped almost immediately with the expectation that patients are eating and drinking within an hour of surgery

  
  
• •
  

  Early mobilization protects against functional decline and the other deleterious effects of bed rest and is possible within an hour of surgery

  
  
• •
  

  Opioid-sparing analgesia is desirable and achievable at discharge with short- and long-term benefits

  
  
• •
  

  Proactive chest tube management using digital devices, with removal based on air leak cessation instead of pleural fluid output, facilitates patient mobilization and effective pain relief

  
  
• •
  

  Mobilization and chest tube removal on the day of surgery is feasible and safe

13

Research agenda

• •
  

  The results of trials looking at the efficacy of perioperative gabapentinoids as an adjunct to conventional analgesia should be available shortly

  
  
• •
  

  Adequately powered RCTs of non-catheter-based regional anesthesia with liposomal bupivacaine versus conventional catheter-based techniques are required

  
  
• •
  

  Prospective trials attempting to correlate early mobilization with a variety of patient outcomes (and ideally making use of wearable technology) would be welcome

  
  
• •
  

  As very little evidence is available to inform chest tube size, the question of whether small chest tubes are effective and safe should be addressed

  
  
• •
  

  Further evidence regarding the logistics and safety of proactive day 0 interventions, in particular mobilization and chest tube removal, are necessary for widespread adoption

CRediT authorship contribution statement

Timothy J.P. Batchelor: Conceptualization, Methodology, Writing – original draft, Writing – review & editing.