Surgery - Preparation and Recovery

Surgery - Preparation and Recovery

1 Overview

Summary and Quick Facts

  • Modern surgical techniques make surgery more effective and safer than ever before. Nevertheless, it’s still important to properly prepare for surgery and take steps to ensure recovery after an operation.
  • This protocol covers what you should do before and after an operation, to promote a healthy recovery. Several emerging techniques that may further improve surgical outcomes are reviewed, as well. Supplements that support the body’s healthy response to the trauma of surgery are also described.
  • Immunonutrition is an important emerging concept in the context of surgical recovery. Supplementation with protein, omega-3 fatty acids such as fish oil, vitamins and minerals has been shown to improve surgical outcomes and shorten hospital stays.

How Can I Prepare for Surgery and Speed Recovery?

Almost 50 million inpatient surgeries are performed each year in the United States. Modern advances have made surgeries faster, more precise, and much safer. Of course, there are still risks associated with any surgery, including infection, pain, and complications from anesthesia.

Recently, several strategies have been identified that patients and their medical teams can utilize to promote faster recovery times and improve patient health.

Also, many natural integrative interventions such as omega-3 fatty acids, coenzyme Q10, and vitamins C, D, and E have been shown to improve patient health both pre- and postoperatively.

What is Important During the Preoperative Period?

  • Risk assessment – the surgical team will determine the patient’s risk of complications and what steps to take to prevent them.
  • Nutritional interventions to ensure the patient has adequate reserves of carbohydrates, proteins, fatty acids, vitamins, and minerals
  • Preoperative fasting to reduce the risk of complications due to anesthesia
  • Premedication to prevent blood clots, if deemed necessary
  • Premedication with antibiotics, if deemed necessary
  • Lifestyle changes such as quitting smoking or exercising to improve outcomes

What is Important During the Postoperative (Recovery) Period?

  • Pain management, either through medication or non-medicinal interventions like massages
  • Wound healing – proper levels of oxygen and nutrients are essential for healing wounds.
  • Preventing infection, potentially with antibiotics
  • Food and fluid intake is necessary for recovery. Patients should focus on food and supplements to boost their immune system and promote healing (see “What Natural Interventions are Beneficial for Surgery Recovery?”).
  • Physical activity as soon as possible after surgery

What Emerging Strategies Appear Promising For Improving Surgery Outcomes?

  • Using natural openings instead of incisions to reach the area of surgery
  • Decreased size and number of incisions (eg, laparoscopic surgery)
  • Robotic surgeries
  • Advances in creating artificial materials and body parts like 3-D printing

What Natural Interventions are Beneficial for Surgery Recovery?

  • Immunonutrition shakes. Several immunonutrition shakes and supplements are commercially available and can reduce the risk of infection and shorten hospital stay. Most effective supplements contain omega-3 fatty acids, proteins and amino acids, and a variety of vitamins and minerals.
  • Vitamin C. Vitamin C is important for wound healing, reducing the incidence of atrial fibrillation, and reducing markers of oxidative stress. The combination of intravenous vitamin C with thiamin (vitamin B1) and hydrocortisone has been shown to significantly reduce the risk of death from sepsis.
  • Vitamin E. Vitamin E can improve wound healing, reduce tissue damage caused by free radicals, and lessen surgically-induced inflammation.
  • Vitamin D. Vitamin D is critical for bone health and can improve patient outcome in certain surgeries including knee replacement and hip fractures.
  • Omega-3 fatty acids. Omega-3 fatty acids may reduce the risk of infection and other complications, shorten hospital stays, and improve the nutritional status of postoperative patients.
  • Coenzyme Q10 (CoQ10). CoQ10 is an antioxidant that may reduce inflammation due to various surgeries.
  • Zinc. Zinc is an important cofactor for several enzymes involved in wound healing.
  • Propolis. Propolis, a resin produced by honey bees, has antimicrobial properties that may help heal wounds.
  • Many other natural interventions may be beneficial to those undergoing surgery, including melatonin, curcumin, alpha-lipoic acid, probiotics, N-acetyl cysteine, and others.

2 Introduction

In the United States alone, almost 50 million inpatient surgeries are performed each year (Stanford Health Care 2017f). These surgeries can range in complexity from removal of benign skin tags to brain surgery. For many patients, surgery is a life-saving event.

Modern surgery is relatively quick, precise, and effective, taking advantage of decades of research and the most advanced technology. With the help of robotics and imaging, incisions can be kept amazingly small for many procedures (Peters 2018; Jacob 2003). In addition, anesthesia practices have become much safer (Botney 2008; Schnittker 2015), and researchers are finding ways to use artificial tissues and organs (Di Bella 2018; McGilvray 2018; Atala 2000). 

In recent years, a whole field of research has been dedicated to finding ways to improve patient recovery after surgery (Steenhagen 2016; Ljungqvist 2017). This research has identified many steps patients and their medical teams can take before, during, and after surgery to optimize the patient's health, improve safety, and speed recovery. For instance:

  • Immunonutrition formulas can boost the patient's immune system to help fight infections and keep inflammation in check (Xu, Sun 2018).
  • Preoperative fasting times can be kept short to maintain the patient's strength and blood glucose levels (Sarin 2017).
  • Physical activity can be initiated soon after surgery to shorten the hospital stay and improve chances of full recovery (Steenhagen 2016; de Almeida 2017).

Several nutritional supplements should be considered by patients preparing for surgery and those in the post-operative recovery period. For instance, nutrients that quench free radicals, such as vitamin C, coenzyme Q10, melatonin, and curcumin, can protect tissues from the oxidative damage associated with surgical procedures (Sadeghpour 2015; Liu, Cheng 2017; Esteban-Zubero 2016; Hewlings 2017). Zinc can help in wound healing (Lin 2017). Whey protein may help improve functional capacity after surgery (Gillis 2016). Omega-3 fatty acids can help inhibit many aspects of inflammation in response to stressful events (Calder 2018; Kiecolt-Glaser 2014).

In this protocol, you will learn about the three phases of surgery: the preoperative period, the surgery itself, and the recovery period. Patients can undertake action that may improve their status during each of these three stages. You will also learn about novel and emerging surgical strategies and ways to improve your nutritional status to speed recovery and enhance the chances of more successful surgery results.

Readers are also encouraged to review the Trauma and Wound Healing. It is important that aging people who plan to undergo surgery review the Immune Senescence protocol as well because immune decline during aging has been associated with altered inflammatory response to surgery. Thus, it may be pertinent, especially for aging people, to take steps to bolster their immune health before undergoing surgery (Zhao 2015). Lastly, readers scheduled to undergo surgery for cancer should also review the Cancer Surgery protocol.

3 The Preoperative Period

In an ideal situation, patients undergoing surgery will have adequate time before the operation to prepare themselves emotionally and physically. The healthier patients are when they go into surgery, the healthier they are likely to be during the postoperative phase. The preoperative period is also a chance for patients to make sure they fully understand the goals and procedural steps of their surgery, as well as the preoperative instructions provided by their healthcare providers. During this period, anxiety about the surgery may be a problem for some people, but patients, along with their surgical teams, can take steps to alleviate this stress.

Risk Assessment

During the preoperative period, surgical teams assess patients for various risks, such as blood clots, malnutrition, and muscle weakness (Dinic 2018; Thiruvenkatarajan 2014; Akhtar 2013). These risks will depend, of course, on the patient's underlying disease, lifestyle, type of surgery, and other health complications the patient may have (Bihorac 2018). Risk assessment tests may include chest X-rays, electrocardiograms, urinalysis, and blood tests (Stanford Health Care 2017g). Once risks are assessed, the medical team can take steps to protect the patient.

Enhanced Recovery After Surgery (ERAS)

The concept of Enhanced Recovery After Surgery, or ERAS, was originally developed when a number of leading surgeons came together to evaluate ways to reduce the number of patients with postoperative complications (Dinic 2018; Xu, Zheng 2018). This group of experts has produced many guidelines for surgical teams and hospitals to improve patient care before, during, and after surgery (Sandrucci 2018; Melloul 2016; Beverly 2017).

The components of the ERAS guidelines are similar to those highlighted throughout this protocol and include measures such as improved preoperative nutrition, reduced preoperative fasting, and early movement after surgery (Dinic 2018). ERAS measures have been shown to reduce hospital stays and rates of complications by about 30% to 50% (Ljungqvist 2017; Eskicioglu 2009; Lassen 2009; Ahmed 2018).

Several hospitals and clinics all over the world have implemented some or all of the ERAS guidelines. For more information on the ERAS society, patient experiences with ERAS, and brochures on various procedures, see the society's website (ERAS Society 2016):

http://erassociety.org/patients

For more information on ERAS guidelines for many types of surgery, see:

http://erassociety.org/guidelines/list-of-guidelines

Nutrition

For many patients, the preoperative period is a time when many nutritional interventions can have a considerable effect. One overlooked statistic is that about 40% of acutely hospitalized patients are malnourished (Barker 2011). Patients with cancer or elderly patients are particularly at risk (Ocon Breton 2017; Favaro-Moreira 2016).

Malnutrition can lead to slow wound healing, suppression of the immune system, and muscle weakness (Stechmiller 2010; Bourke 2016; Lunardi 2012). ERAS guidelines recommend that nutritional status of all patients be evaluated before surgery and patients should be given enteral nutrition (tube feeding) not when they become malnourished, but when the risk of malnutrition becomes apparent (Weimann 2006).

A healthy diet and appropriate nutritional supplements can help prepare a patient for surgery by maximizing reserves of proteins, essential fatty acids, vitamins, and minerals. Specific nutrients and supplements can also help bolster the immune system, minimize oxidative damage, and keep inflammation under control. For more information on specific nutritional interventions, see the “Integrative Interventions” section of this protocol.

Preoperative Fasting

Practically since the inception of general anesthesia for surgery, doctors have worried about the effects of a full stomach during anesthesia. The chief risk is that patients will aspirate stomach contents into their lungs, which may cause severe inflammation, infection, or even death (Sarin 2017). Modern anesthesia practices, however, such as careful control of the patient's airways, close monitoring, and selective use of appropriate anesthetic drugs, have dramatically reduced this risk (Powers 2017; Michalek 2014). Because of delays and changes in operating room schedules, patients often end up fasting for 12 hours or more, and the metabolic response to fasting intensifies the response to the trauma caused by the surgery (Pimenta 2014).

Increasingly, anesthesiologists are recognizing both the biological and psychological value of permitting patients a reasonable oral intake. Modern recommendations have significantly reduced fasting periods (Sarin 2017; American Society of Anesthesiologists 2017). For instance, the American Society of Anesthesiologists guidelines state that for healthy patients undergoing elective procedures, a light meal such as toast and a clear liquid is acceptable until six hours before surgery (American Society of Anesthesiologists 2017). Clear liquids (tea, fruit juices without pulp, water) are acceptable until two hours before surgery. Patients should discuss preoperative fasting with their physicians well in advance of surgery.

Carbohydrate Treatment

As data have emerged supporting reduced preoperative fasting times, other studies have addressed whether a carbohydrate-rich supplement before surgery can improve patient outcomes (Weimann 2006; Jankowski 2017; Evans 2014). Surgery stresses the body and changes the patient's metabolism (Finnerty 2013), causing a catabolic state. In a catabolic state, the body starts breaking down proteins, leading to muscle wasting and suppression of the immune system. For some patients, a carbohydrate-rich drink two to three hours before surgery can prevent the body from entering this altered metabolic state (Jankowski 2017). Meta-analyses found that preoperative carbohydrates reduced surgery-induced insulin resistance and the length of time patients had to stay in the hospital (Awad 2013; Smith 2014).

Glucose Control

Both low and high glucose levels can be problematic during the perioperative period. Studies indicate that surgery-induced insulin resistance, leading to elevated glucose levels during surgery, occurs in up to 60% of surgery patients and raises the risk of complications and death (Galindo 2018; Duggan 2016). Intensive insulin therapy, a procedure in which glucose levels are closely monitored and maintained during surgery, can help reduce complications and lower the risk of death (Trussell 2008; van den Berghe 2001; Galindo 2018). However, this practice is not standard in hospitals and requires intensive monitoring by nurses and other members of the surgical team. Nevertheless, because of the benefits, patients may want to discuss intensive insulin therapy with their surgical team to see if it is warranted in their situation.

Oral Immunonutrition

Surgery and the underlying medical condition can suppress a patient's immune system just when optimal immune function is most important. Researchers are investigating ways to boost the immune system with various preoperative nutritional supplements collectively referred to as immunonutrition (Jankowski 2017; Gupta 2017). These formulas are flavored drinks or shakes produced by different companies and available without a prescription from stores such as Walmart and Amazon or directly from the manufacturers.

The purpose of immunonutrition shakes is to provide the proper nutrient mix to boost healthy immune function while suppressing exaggerated inflammatory responses (Song 2017; Hammad 2017). Each immunonutrition product contains a variety of ingredients. For example, two well-studied immunonutrition formulas called Oral Impact (Nestle Health Science) and Ensure Surgery (Abbott Nutrition) contain omega-3 fatty acids, protein and DNA building blocks, vitamins, and minerals. A study that used Oral Impact reported an increased activation of T cells and antigen presenting cells in the tissue of patients scheduled for surgery (Scarpa 2017). In one study of over 3,000 surgical patients, Oral Impact, taken before surgery, was associated with a lower chance of a prolonged hospital stay (Thornblade 2017).

For more information on components of immunonutrition formulas, see the “Integrative Interventions” section of this protocol.

Anxiety

Most people who will be undergoing a surgical procedure, no matter how minor, have some degree of anxiety about the procedure, its outcomes, and potential complications. A notable degree of anxiety can occur in up to 80% of patients (Sheen 2014). Patients report the fear of losing control during surgery, some are concerned that they will not be able to wake up, and some express their fear of pain (Hernandez-Palazon 2018). Psychological and emotional stress reduces the body's immune function and renders people more vulnerable to disease (Segerstrom 2004; Marshall 2011). Preoperative anxiety is also associated with high levels of pain after surgery (Thompson 2008; Ip 2009).

Preoperative anxiety can be alleviated in several ways. The most important is patient education and counseling. When doctors educate patients about their medical conditions, surgical procedures, and recovery, patients feel less anxiety (Wongkietkachorn 2018; Lee 2017). A face-to-face meeting or phone call with the anesthesiologist can be particularly helpful. Printed materials, online materials, or personal counseling have all been shown to be effective, as long as patients get the information they need (Jankowski 2017; Ayyadhah Alanazi 2014). For example, in a randomized clinical trial of 100 patients scheduled for surgery, watching an educational video on anesthesia was associated with a significant reduction in patient-reported anxiety and an increase in patient satisfaction (Lin 2016). Many patients effectively alleviate their own anxiety by searching for information on the internet, although it is important that the sources of information be reputable and reliable (Tulgar 2017).

Another way to reduce anxiety is to keep the preoperative period reasonably short. The preoperative period should be just long enough to optimize the patient's health before going into the procedure. Excessively long preoperative periods, however, may be associated with increased amounts of worrying, anxiety, and stress; these factors can have a negative impact on surgical outcomes (Shoar 2016). Similarly, keeping the preoperative hospital stay as short as possible can also reduce anxiety (D'Andrilli 2018).

Integrative medicine strategies for reducing preoperative anxiety and stress have been shown to be helpful in varying degrees (Attias 2016). Hypnosis has been found to be effective in reducing both preoperative and postoperative anxiety (Kendrick 2016; Akgul 2016). A related technique called guided imagery, in which a skilled therapist works with the patient to envision low-stress and positive concepts, has also been documented to reduce anxiety, safely lower pulse and blood pressure, and shorten hospital stays (Hadjibalassi 2018; Halpin 2002; Norred 2000). Relaxing music or aromatherapy with essential oils may also be helpful (Ayik 2018; Wotman 2017; Franco 2016; Millett 2018). Some studies are even exploring virtual reality to help surgery patients relax (Ganry 2018).

Premedication

Patients undergoing surgery are at increased risk of blood clots during and after the procedure. Depending on the type of procedure and the patient's medical history, doctors may recommend medications to help reduce the risk of blood clots (Childers 2018; Bell 2015; Moffatt-Bruce 2017). For instance, in patients undergoing surgery to repair a broken bone, only one of 39 (2.6%) patients treated with the anti-clotting drug rivaroxaban (Xarelto) had a type of blood clot called a deep vein thrombosis after surgery, compared with eight of 41 (19.5%) who did not take the drug (Li 2017).

Aspirin is well-known for reducing blood clots. Some studies suggest low-dose aspirin may benefit certain patients, such as those undergoing coronary artery bypass surgery, when taken within 24 hours before surgery (Deng 2015). However, because aspirin's effect on clotting may increase the risk of bleeding, patients should not begin aspirin therapy unless under the direct supervision of their surgical team. Lower doses (less than 100 mg per day) may not increase the risk of bleeding based on some research, but additional studies are required (Ma 2014).

Some patients may also be treated with antibiotics before surgery to reduce the risk of infection (Chang 2012; Holubar 2017). Certain procedures, such as surgeries on the gastrointestinal or respiratory tract, are associated with a higher risk of infection. The type of antibiotic prescribed will depend upon the bacterial strains present at the site of surgery (D'Andrilli 2018). When developing guidelines for the use of antibiotics before surgery, doctors are careful to balance the risk of infection with the risks associated with antibiotic use, such as adverse effects or antibiotic resistance (Bryson 2016).

Lifestyle

Patients who smoke do not fare as well during and after surgery (Turan 2011; Musallam 2013). Doctors recommend that smokers stop smoking at least eight weeks before their surgery if possible, and there is strong evidence that smoking cessation reduces the risk of complications and death after surgery (Thomsen 2014; Sorensen 2012; Rodrigo 2000; Singh 2013).

Some patients may also benefit from efforts to improve physical functioning prior to surgery. For patients who will undergo lung surgery, preoperative breathing exercises may help maximize lung function prior to surgery (Kendall 2017). Frailty prior to surgery is associated with poor patient outcomes (Mosquera 2016; Arya 2015). Thus, an exercise program with aerobic exercise and strength training may be helpful to some patients if they are healthy enough to exercise (Mainini 2016).

4 The Operation Itself

In the past, surgery almost always involved large incisions, heavy anesthesia, and relatively long procedures. But with modern advances, surgical procedures have become safer, quicker, and less invasive, allowing patients to recover more quickly.

Types of Surgery

In recent years, surgeons have found many ways to make surgery less invasive. Traditional surgery, where the skin and underlying tissues are cut through with a scalpel, is called open surgery. Recovery after open surgery is generally longer than recovery after less invasive procedures, and patients are more likely to have complications during recovery (Fan 2018). While in the past open surgery used to be the only option for some surgical interventions, in recent years it has been increasingly replaced by minimally invasive surgery (Langer 2016; Doenst 2017; Stanford Health Care 2017b; Salem 2018; Sood 2015).

When the medical issue can be addressed without open surgery, surgeons use a less invasive technique such as a laparoscopic procedure (Mayo Clinic 2017). Laparoscopic surgery is a type of minimally invasive surgery that uses smaller incisions (Nezhat 1992; Ross 2009). A long, thin instrument called a laparoscope is inserted into a small hole to allow the surgeon to see the target area (Stanford Health Care 2017a). Additional instruments are inserted through the same or other small incisions. Patients having minimally invasive surgeries, such as laparoscopic surgery, lose less blood, have fewer infections, and go home sooner than patients having open surgery (Wang 2017; Xiong 2017; Huang 2013).

Laparoscopic surgery is commonly performed to correct problems in the abdomen, but surgeries in other parts of the body have also become less invasive with the help of imaging. Video-assisted thoracoscopic surgery procedures use a tiny camera inserted through small incisions to guide surgeries in the chest area (Xu 2013; Dziedzic 2015). Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) can all be used in image-guided surgeries to help surgeons carefully target the intended area and avoid healthy surrounding tissues (Tringale 2018; Jenkinson 2018; Stammes 2018).

Doctors can perform some surgeries with the help of robots (Mayo Clinic 2018b). Robotic surgery requires only tiny incisions and can help the surgeon control the instruments with more precision (Peters 2018). Robotic procedures may lead to less blood loss (Ilic 2017) and fewer complications (Kim 2018; Barrie 2016).

Lasers are a valuable tool for some surgical procedures. Lasers create a concentrated beam of energy that can cut through some types of tissue (Stanford Health Care 2017b). Surgeries on delicate tissues and organs, such as the eyes, can use lasers instead of traditional cutting tools. Lasers can also be used to directly repair some problems. For instance, lasers can be used to remove plaque from an artery, repair gums, or treat small stomach tumors (Sobouti 2015; Azadgoli 2016; Livesay 1984).

More extensive surgical procedures may require the patient to stay one or more nights in the hospital (Stanford Health Care 2017e). These are called inpatient surgeries. With modern advances, procedures have become far less invasive and recovery from anesthesia is quicker. More patients can go home the same day as the surgery (Stanford Health Care 2017c). These are called outpatient or ambulatory surgeries.

Types of Anesthesia

The type of anesthesia required will depend in part on the type of surgery the patient is undergoing. A surgery affecting a small area of the body, particularly on or near the skin, may require only local anesthesia (Stanford Health Care 2017h; Mutalik 2008; Skidmore 1996). The patient is numbed in only a small area, and over time the anesthetic wears off.

For some procedures affecting larger parts of the body, anesthesiologists may be able to target the nerves from the area undergoing surgery (Stanford Health Care 2017h; Wahal 2018). This is called regional anesthesia. Regional anesthesia is often used for surgeries on the arms and legs, Caesarean section, and certain procedures in the bladder or urinary tract (ASRA 2018).

Patients can remain awake with regional anesthesia, but a sedative may also be used to keep the patient comfortable (ASRA 2018). Sedation can range from minimal to deep. Because sedatives can slow the patient's breathing, an anesthesiologist monitors the patient's vital signs carefully to avoid any complications.

Under general anesthesia, the patient is unconscious throughout the procedure (Stanford Health Care 2017h). The anesthesia affects the whole body. After the procedure, the patient wakes up in the recovery room with no memory of the procedure.

Although complications with anesthesia can be severe, they have become rare with advances in anesthesia practices (Botney 2008; Schnittker 2015). Anesthesiologists plan the array of medications carefully to minimize negative effects. They also carefully monitor their patient's blood pressure, heart rate, and blood oxygen levels throughout the surgery (Merry 2010). With sedation or general anesthesia, proper breathing may be maintained with oxygen, lung ventilation, and breathing tubes.

Table 1: Types of Anesthesia

Type of Anesthesia

Description

Local

  • An anesthetic agent is applied to the skin or injected into the affected site.
  • The patient remains conscious.
  • Used for minor surgery to an area that can be easily accessed.

Regional

  • An anesthetic agent is injected near a specific nerve to block sensations of pain from the target area.
  • Includes spinal, epidural, and peripheral nerve block.
  • The patient remains conscious and the anesthetic wears off after the procedure.
  • Can be used along with a sedative.

General

  • An anesthetic agent is given through a breathing mask or tube or through an IV.
  • Patient is unconscious throughout the surgery.
  • After the procedure, the patient wakes up in the recovery room.
  • Used for long procedures or those that may affect breathing or lead to blood loss.
  • Breathing may be managed using a tube into the wind pipe or an airway mask.

Blood Transfusions

Surgical techniques have been improved to try to reduce the need for blood transfusions (Carabini 2018; Stoneham 2017). If the medical team believes a patient may need a blood transfusion during an upcoming surgery, the patient may donate blood ahead of time so their own blood will be available during the procedure (Boer 2018). This is called an autologous transfusion. Blood transfusions have been associated with many complications, including an increased risk of heart rhythm problems (Liu 2018) and kidney failure (Paone 2014) in patients undergoing heart surgery and a higher risk of postoperative death (Lee 2018; Crawford 2018). Massive blood transfusions can have untoward effects, especially with regard to calcium status (Giancarelli 2016).

Oxygen Supplementation

The oxygen provided during surgery may itself be a mixed blessing. A sufficient supply of oxygen to the surgical site is critical for maintaining normal cellular processes and for proper wound healing. However, supplemental oxygen, when used at high concentrations, may also produce increased levels of reactive oxygen species, which may cause harmful inflammation and can damage tissues (Francis 2017; Martin 2015; Dikmen 2017). Although an inflammatory response is necessary during the first stages of healing, sometimes when it becomes accentuated after surgery, as a result of depressed immunity, it may lead to complications such as infections (Angele 2005).

During cardiac bypass surgery and some other surgeries, blood flow to the area where the surgery is performed is restricted with surgical clamps. When the clamps are removed, blood flows into the surgical area again. Studies have shown that if the blood oxygen level is too high when the clamps are removed, the tissue can be damaged (Inoue 2002; Sepehrvand 2016). Also, patients with high oxygen levels (hyperoxia) are at an increased risk for needing mechanical ventilation and acquiring an infection (Jakutis 2017).

Prevention of Blood Clots

Deep vein thrombosis (DVT) occurs when a blood clot forms in a deep vein, typically in the leg (Mayo Clinic 2018a). Blood cannot exit the limb properly, and the limb may start to swell. If the clot or pieces of it break free, they can travel through the bloodstream to the lungs, where the effects are more dangerous (Sogaard 2014).

Surgical patients are at increased risk of DVT due to medications given during surgery, lack of mobility for hours or days or, sometimes, underlying medical conditions (Osaki 2017; Aibinder 2018). During surgery, compression stockings or devices that fill with air to compress the lower legs may help patients at risk for DVT (Bell 2015; Sederino 2016; Elbuluk 2018).

Surgical Team

During a surgical procedure, there are several medical professionals in the operating room. The surgeon performs the surgery, typically assisted by one or more registered nurses that specialize in surgery (Stanford Health Care 2017i). The anesthesiologist is responsible for the anesthesia plan and monitors the “ABCs,” or airway, breathing, and circulation, during surgery (Becker 2007). A certified registered nurse anesthetist will often assist the anesthesiologist. Surgical technicians may carry out various duties before, during, and after the operation to assist the rest of the operating staff and patient.

5 The Postoperative (Recovery) Period

Pain

When patients first recover from anesthesia, they may feel groggy and confused as the drugs wear off. Nausea is a common side effect of many of the medications used during surgery. After these initial symptoms, the patient's primary complaint is typically pain. The medical team monitors the patient's pain level to find a medication plan that improves the patient's comfort level without limiting the patient's ability to move or eat (Nimmo 2017). Many hospitals are also trying to reduce the use of opioids, which can become addictive (Grant 2017).

Excellent preoperative care and nutrition to prepare the patient for surgery can reduce the amount of pain the patient experiences after surgery (Sarin 2017; Kratzing 2011). Non-medicinal interventions can also be helpful for alleviating pain. Even a single massage was shown to significantly reduce pain after some procedures (Kukimoto 2017). Hypnosis and guided distraction/imagery can decrease both pain and anxiety after surgery (Duparc-Alegria 2018; Abdeshahi 2013; Davidson 2016; Tusek 1997).

Wound Healing

A certain amount of inflammation is necessary for proper wound healing. Cytokines and other inflammatory mediators are required for building a sufficient blood supply to the healing and newly forming tissue (Lin 2017; Boniakowski 2017; Gharaee-Kermani 2001; Barrientos 2008). Inflammatory cells are also required to fight infections; however, excessive inflammation can also impair the healing process (Boniakowski 2017; Smith 2017; Xu 2017).

Supplemental oxygen, a very frequent part of postoperative treatment, ensures that adequate oxygen is available to rapidly healing tissue (de Smet 2017; Gottrup 2017). Wound healing is known to be accelerated by moderately elevated tissue oxygen levels (Guo 2010; Chambers 2011). Doctors are also exploring how to use oxygen to fight infections in surgical wounds (Dryden 2017; Dunnill 2017). However, very high oxygen levels can damage tissue in the wound site (Andre-Levigne 2017; Bhutani 2012). Micronutrient supplementation and good nutrition have been shown to promote surgical wound healing (Ellinger 2014).

Pressure ulcers, or bedsores, are a type of wound that may develop at pressure points in patients who are unable or unwilling (because of pain) to shift their positions in bed (Atkinson 2018). Constant pressure reduces local blood flow, producing ischemia (reduced oxygen levels), lack of nutrients, and eventually cell death (Akbari 2014; Agrawal 2012; Kruger 2013). Areas of dead and dying tissue can be a breeding ground for bacteria.

Prevention of pressure ulcers is one of the chief priorities of the medical team in the postoperative period. Poor nutritional status is a major risk factor for pressure ulcer development (Lussi 2018; Taylor 2017), and many nutritional interventions have been shown to be helpful (Karahan 2018; Cox 2014). Supportive mattresses, frequent repositioning, and special wound dressings may help prevent and treat pressure ulcers (Boyko 2018; Serraes 2018; Elsabrout 2018).

For additional information on wound healing, see the Trauma and Wound Healing protocol.

Food and Fluid Intake

Enhanced recovery after surgery protocols emphasize optimal nutrition and maintaining an adequate fluid balance (Steenhagen 2016). For most types of surgery, patients should be able to eat and drink on the day of the surgery (Ljungqvist 2017). Energy needs and requirements for nutrients increase after surgery (Ellis 1991; Wischmeyer 2018; Demling 2009; Finnerty 2013). By maximizing nutrition and caloric intake, patients heal and recover faster (Demling 2009; Russell 2001; Wild 2010; Gruen 2010).

Before, during, and after surgery, patients typically receive IV fluids to compensate for fluids lost during the procedure. Too much IV fluid can be harmful to the patient, leading to swelling and organ damage (Sweeney 2013; Steenhagen 2016). Well-trained medical teams are able to find the right balance (Ramsay 2018). In many cases, limiting postoperative IV fluids can shorten hospital stays and improve recovery (Onyekwelu 2016).

The recovery period is an excellent time to optimize nutrition in the diet. Patients should focus on foods and supplements that can boost the immune system and promote wound healing. For some patients, immunonutrition formulas may be helpful (Xu, Sun 2018; Probst 2017; Song 2017). For more information on immunonutrition, see the “Integrative Interventions” section of this protocol.

Physical Activity

Patients should begin moving around as soon as possible after surgery (Steenhagen 2016). Programs to actively encourage movement may be helpful. In one study of patients undergoing abdominal surgery for cancer, 38.9% of those treated with standard care were unable to walk unassisted five days after surgery versus 16.7% of those participating in a supervised program of strength, flexibility, and aerobic training (de Almeida 2017). Prolonged bed rest can increase the risk of deep vein thrombosis (DVT), muscle weakness, and poor wound healing (Steenhagen 2016; Grey 2006). Even lying in bed, patients can help prevent DVT by moving their legs in a bicycle motion or tracing letters in the air with their toes (Stanford Health Care 2017d).

For patients undergoing lung surgery, postoperative breathing exercises may be beneficial (Stanford Health Care 2017d). Medical teams may teach recovering patients how to take deep breaths and safely cough (while supporting the incision) help remove chest secretions and prevent pneumonia. Specific exercises called inspiratory muscle training, or IMT, can improve blood oxygen levels after surgery (Brocki 2016).

Postoperative Cognitive Dysfunction

Acute confusion and impaired consciousness within a few days after major surgery is quite common, especially among older adults. This phenomenon is called postoperative delirium, and typically resolves before hospital discharge (Whitlock 2011). Whether or not general surgery under anesthesia directly causes long-term cognitive problems—termed postoperative cognitive dysfunction—is less clear. While there may be a true effect in some people, current evidence suggests surgery and anesthesia are not robustly and directly linked to long-term cognitive impairment in most patients (Tsai 2010; Rundshagen 2014; Avidan 2016).

Ongoing research has not found strong evidence of a link between persistent cognitive deficits and major surgery independent of overall health of the patient and their cognitive status trajectory before surgery (Avidan 2016; Aiello Bowles 2016; Dokkedal 2016). Predisposing factors to worse cognitive outcomes after surgery include preexisting low-grade cognitive decline and early Alzheimer-type changes (Rundshagen 2014; Berger 2015). Observational evidence linking surgery to cognitive decline is relatively weak, and rigorous study data suggest any true effect on long-term cognitive function is likely negligible (Dokkedal 2016; Jiang 2017). It may be that much of the apparent decline in cognitive function observed after surgery in older people is attributable to the post hoc ergo propter hoc fallacy—“after this, therefore because of this.” But the expected continuation of a preexisting cognitive decline trajectory is thought to be the true culprit in many cases (Avidan 2016).

One study found that, in pairs of middle-aged to elderly twins—who have very similar genetic and biochemical susceptibility—when one had undergone major surgery and the other had not, their cognitive scores were nearly identical. Another analysis in this study compared the twin who underwent surgery to a control group and found a small, clinically insignificant tendency to a lower cognitive score (Dokkedal 2016). In a meta-analysis that pooled data from 19 studies, no clear association was found between general anesthesia and dementia risk. Nevertheless, when the analysis was limited to studies that used records of anesthesia rather than subjective patient recall, the authors found a small increased risk of dementia in those who had received general anesthesia, highlighting the need for high-quality study designs when this phenomenon is studied in the future (Jiang 2017).

The current lack of evidence does not mean that post-operative cognitive dysfunction is not worthy of a clinician's attention. Some studies have indeed found that surgery and general anesthesia are associated with negative effects on cognition in the elderly (Evered 2017; Schenning 2016), negatively impacting the brain's immune system (Schenning 2016), and that post-operative cognitive dysfunction that persists three months after surgery is associated with an increased risk of dying from any cause (Steinmetz 2009). As surgical trauma induces a body-wide surge in inflammation, it has been proposed that inflammation of the brain, and failure to promptly resolve inflammation, may be causative factors for this syndrome. It has been proposed that measures to mitigate the trauma and inflammation resulting from major surgery may help prevent this problem (Rundshagen 2014; Berger 2015).

Novel treatments for preventing post-operative cognitive dysfunction (POCD) are currently under investigation. Perhaps one of the best-studied ones is ulinastatin, an enzyme-inhibiting agent that can be either synthesized or isolated from human urine (Jiang, Hu 2016). It is used in several Asian countries, but not yet approved in the United States (Liu, Yu 2017). A 2016 review of the scientific literature found five randomized controlled trials examining intravenously-administered ulinastatin’s effect on POCD. In these trials, which enrolled a total of 461 elderly patients, ulinastatin reduced POCD compared to control treatment at three and seven days after surgery, but not on the day immediately following the procedure. Ulinastatin also reduced levels of the pro-inflammatory cytokine interleukin-6 within two days after surgery (Lv 2016). A 2017 controlled clinical trial confirmed these results. In this study, 80 elderly patients receiving chemotherapy and undergoing radical esophagectomy were randomized to ulinastatin or a control group. Those in the ulinastatin group experienced less POCD seven days after surgery, an effect the authors hypothesized might have resulted from the observed lower levels of interleukin-6 and C-reactive protein, and higher levels of the protective cytokine interleukin-10 (Wang, Yang 2017).

Two natural interventions have attracted attention for the prevention of POCD. In a randomized controlled trial, 61 patients aged 30‒70 years undergoing cardiopulmonary bypass received either 2 capsules of a Valeriana officinalis root extract per day or placebo. The intervention started a day before surgery and continued until 60 days after surgery. Subjects treated with the root extract had a significantly lower likelihood of POCD than those in the placebo group (Hassani 2015). A second intervention trial, underway as of mid-2018, is evaluating the potential of N-acetylcysteine as a treatment for POCD (Skvarc 2016).

Many of the integrative interventions discussed in this protocol that may help promote surgical recovery may also help promote healthy postoperative cognitive function. Also, refer to the Age Related Cognitive Decline protocol, which reviews many integrative interventions that may support brain health.

6 Novel and Emerging Strategies

Modern surgeries are faster, more precise, and more effective than ever before, but new techniques are being developed that will make surgery even less invasive. One approach is to use the body's natural openings to access internal parts of the body. For instance, surgeons are exploring ways to operate on the thyroid through a patients mouth (Sivakumar 2018) or the gallbladder through a patient's vagina (Benhidjeb 2018).

A second approach to making surgery less invasive is decreasing the size of the incision or number of incisions. Researchers are developing robots that surgeons can control to access the affected area without needing a large incision (Isaac-Lowry 2017). Some laparoscopic surgeries that normally used to require more than one incision can now be performed with only one incision (Binet 2017).

In addition to making surgery less invasive, robots may also minimize human errors and make surgery more precise (Peters 2018). Although traditional robots are made from rigid materials, researchers are finding ways to use soft materials to improve dexterity (Diodato 2018). Some researchers are even developing robots that can perform surgical tasks on their own—the surgeon only preprograms the surgery and supervises the procedure. One of these robots, called smart tissue autonomous robot or STAR, has been shown to make fast and precise incisions, suture incisions consistently, and even remove tumors (Opferman 2017; Shademan 2016). Telesurgery has also been made possible by robots and modern high-speed data services. In telesurgery, patients can be operated on by a surgeon theoretically anywhere in the world. The surgeon operates a surgical robot from a control suite connected to a high-speed data feed from the surgical robot, allowing the surgeon to perform detailed, carefully executed surgery from a distance.

Advances in artificial materials and body parts will also dramatically improve surgical options and outcomes. Artificial heart valves have been an option for decades for many patients needing heart valve replacement (AHA 2016; Dasi 2009), and artificial joints are used for knee or hip replacement (Carr 2012). Now, surgeons are exploring ways to use three-dimensional (3-D) printed bones and other tissues to create new parts for surgery (Di Bella 2018; Yang 2018; McGilvray 2018). 3-D printed models of target organs or tissues can also be made for each patient to help a surgeon optimize the surgical plan ahead of time or design custom prosthetics (Sun 2018; Li 2018).

Surgery and Sepsis

All surgeries run the risk of exposing patients to infections. One of the most feared consequences of surgery-associated infection is sepsis. Sepsis occurs when the immune response to infection leads to catastrophic systemic inflammation, often culminating in organ failure and death (Sepsis Alliance 2017).

Although sepsis can arise from many kinds of wounds or infections, about 30% of cases arise in surgical patients. This means that patients scheduled to undergo surgery should be aware of the risks of sepsis, and should also know about intriguing new evidence that suggests a combination of intravenous vitamin C, thiamine (vitamin B1), and hydrocortisone may offer improved outcomes in sepsis treatment.

In a retrospective study published in 2017, Dr. Paul Marik and his team at Eastern Virginia Medical School reported remarkable success in treating sepsis with IV vitamin C, thiamine, and hydrocortisone (Marik 2017). The study consisted of two groups, with 47 sepsis patients enrolled consecutively in each group over sequential seven-month periods. The treatment group received the IV vitamin C, thiamine, and hydrocortisone combination, and the control group received standard care.

In the control group, 19 of the 47 patients died in the hospital. In contrast, only 4 of the 47 patients in the treatment group died, representing an astonishing 87% relative reduction in the risk of death from sepsis.

Several large randomized clinical trials are recruiting at the time of this writing (ie, May 2018) to verify these effects in rigorous fashion. If these trials prove as successful as Dr. Marik's early efforts, the result could be a revolution in sepsis treatment that saves millions of lives.

7 Integrative Interventions

Modulating immune function to achieve a proper balance of host defenses against infection, while minimizing exaggerated inflammatory responses to surgery, is an important goal of integrative interventions in the perioperative and wound healing settings. Adequate protein intake prior to surgery provides the soon-to-be-healing body with building blocks of new tissue. Optimal micro- and macronutrient intake can be achieved with a reasonable program of supplementation and good dietary habits in the weeks prior to surgery.

Immunonutrition

The advantages of drinking immunonutrition shakes before surgery have been discussed in the preoperative section of this protocol. Patients may also benefit from drinking immunonutrition shakes after surgery. Immunonutrition formulas helped patients get fewer infections and have shorter stays in intensive care and fewer overall hospital days (Xu, Sun 2018; Bharadwaj 2016; Palma-Milla 2018; Scislo 2018). Immunonutrition shakes may also improve wound healing (Celik 2009; Lorenz 2015).

Although many different mixtures of nutrients have been used in immunonutrition formulas, several main components appear to provide maximum benefits. Most immunonutrition preparations contain healthy fats such as omega-3 fatty acids, proteins and their amino acid building blocks, and a variety of vitamins and minerals (Chow 2014; Bharadwaj 2016).

Most effective immunonutrient supplements contain substantial quantities of omega-3 fatty acids. Omega-3 fatty acids are polyunsaturated fatty acids, largely derived from fish oils. These fatty acids can shift the production of cytokines away from those that stimulate inflammation (Ventro 2017; Calder 2017). They also make cell and mitochondrial membranes more resistant to oxidative stress (Calder 2017), which reduces tissue damage and prevents amplification of the inflammatory response. A diet enriched with fish oil has been shown to help treat pressure ulcers (Theilla 2012).

Immunonutrition preparations also often contain arginine and glutamine (Bharadwaj 2016; Chow 2014). These amino acids are described as conditionally essential, which means that under certain stressful conditions (including trauma and surgery), the body cannot synthesize them in normal amounts; it must therefore rely on supplemental sources (Nieves 2002; Albaugh 2017; Hall 1996).

The amino acid arginine provides a substrate for nitric oxide production, which enhances blood flow by relaxing blood vessels and promotes the synthesis of collagen used in wound healing (Chow 2014). It also stimulates and activates immune system cells and helps T cells proliferate (Bharadwaj 2016). Trauma, surgery, and oxidative stress increase the levels or activity of the enzyme arginase, which reduces arginine levels (Engelen 2017; Ochoa 2000; Chandra 2012). Arginine supplementation may enhance wound healing, particularly in combination with omega-3 fatty acids (Alexander 2014) and may help heal pressure ulcers (Liu, Shen 2017; Cereda 2015).

The amino acid glutamine is a major component of proteins produced during clotting (Weisel 2005) and a source of energy for immune cells (Chow 2014). It can also help control the effects of inflammation, primarily by increasing levels of heat shock proteins, which protect cells from stress (Chow 2014; Hartmann 2017; Jordan 2016).

Vitamin C

Vitamin C, which is included in some immunonutrition preparations, is an antioxidant required for the synthesis of certain proteins, making it indispensable in wound and fracture healing. Several studies showed that a better vitamin C status may protect against fractures (Aghajanian 2015; Moores 2013). In patients with wrist fractures, vitamin C supplementation (500 mg per day) was helpful in relieving pain (Zollinger 2007).

Vitamin C may be especially helpful for patients undergoing heart surgery. In one randomized study, patients undergoing heart surgery were treated with either a placebo or vitamin C (2 grams intravenously just before surgery and 1 gram per day orally for four days after surgery). The vitamin C group had shorter hospital stays and shorter intubation times (Sadeghpour 2015).

After coronary artery bypass surgery, many patients suffer from abnormalities in their heart rhythm called atrial fibrillation that can be dangerous. Inflammation and oxidative damage is one contributing factor (Boos 2006). Fortunately, vitamin C may help reduces markers of oxidative stress after coronary artery bypass surgery (Safaei 2017).

Three meta-analyses have been published recently that combine data from multiple clinical trials testing the effects of vitamin C on the incidence of atrial fibrillation after coronary artery bypass surgery (Baker 2016; Hu 2017; Polymeropoulos 2016). In most of the trials, patients were treated with 2 grams of vitamin C within 24 hours before surgery and 1 gram per day for several days after surgery. All three meta-analyses found that vitamin C supplementation significantly reduced the incidence of atrial fibrillation.

Vitamin E

Vitamin E is a potent antioxidant and fat-soluble vitamin found in large amounts in the skin, where it may improve wound healing and scar appearance (Hobson 2016; Zampieri 2010). By scavenging reactive oxygen species, vitamin E can reduce tissue damage caused by free radicals, thereby reducing surgically induced inflammation (Souyoul 2018). Vitamin E levels are depleted during surgical procedures, especially those that require use of a heart-lung machine (Schindler 2003; Valle-Giner 2007).

A 2017 study found that vitamin E applied under the skin of the surgical incision site helped reduce the rate of surgical site infections among patients having surgery for colorectal cancer, and decreased pain after surgery (Alias 2017). Vitamin E supplementation may also help bones heal. In animal models, supplements containing vitamin E promoted fracture healing (Shen 2017; Ibrahim 2014). In humans, vitamin E (1,000 IU per day) may help repair bone damage that occurs after radiation treatment (Delanian 2005; Aggarwal 2017).

Vitamin D

Vitamin D is critical for bone health, including bone formation and maintenance, and may be particularly important for patients undergoing orthopedic surgery (Turner 2012; Gennari 2001; Mabey 2016; Rodriguez 2013). An analysis of people scheduled for orthopedic surgery found that low levels of vitamin D affected about 40% of patients (Bogunovic 2010). Vitamin D supplementation was found to significantly improve functional recovery among patients undergoing knee replacement (Maniar 2016), and vitamin D supplementation improved the quality of life among patients recovering from surgery to repair a hip fracture (Sprague, Slobogean 2017). A study on elderly patients who underwent surgery for hip fracture found that only about 39% of the patients took vitamin D supplements consistently (Sprague, Madden 2017).

Omega-3 Fatty Acids

Omega-3 fatty acids have already been discussed as a critical component of immunonutrition formulas, but omega-3 fatty acids and fish oils have also been studied outside of that context. Supplementation with omega-3 fatty acid rich fish oil may reduce the risk of infection and other complications, shorten hospital stays, and improve nutritional status and liver and pancreatic function in postoperative patients (Calder 2018; Heller 2004; Ma 2016). A meta-analysis and review of evidence on patients who underwent surgery for gastrointestinal cancers reported that omega-3 fatty acids improved nutritional status, improved immune function, and decreased inflammation (Yu 2017). In patients undergoing heart surgery, supplementation with omega-3 fatty acids (2 to 10 grams per day) decreased the length of hospitalization and risk of certain heart rhythm problems after surgery (Langlois 2017). Moreover, omega-3 fatty acids may reduce the risk of death after abdominal surgery and improve recovery (Zhang 2017; Tsekos 2004).

Fish oil supplements may reduce the exaggerated inflammatory response that accompanies surgery (Ma 2015; Aiko 2005; Wang 2016). Among 861 patients recovering from kidney transplant, those with low levels of omega-3 fatty acids in their plasma had the highest levels of proinflammatory cytokines (Eide 2017).

Coenzyme Q10

Coenzyme Q10 (CoQ10) is an antioxidant molecule intimately involved in energy production in cells (Saini 2011; Deichmann 2010). CoQ10 levels plummet markedly after surgery, presumably because of rapid consumption by oxidant species (Liu, Cheng 2017; Pechan 2004). In a randomized placebo-controlled clinical trial, a dose of 300 mg per day of CoQ10 improved antioxidant capacity and reduced inflammation in patients undergoing surgery for liver cancer (Liu 2016). Supplementation with CoQ10 has been associated with a significant decrease in the proinflammatory cytokines tumor necrosis factor-alpha, C-reactive protein, and interleukin-6 (Zhai 2017; Fan, Feng 2017).

Supplementation with CoQ10 has been shown to reduce mortality and improve exercise capacity in people with heart failure (Lei 2017; DiNicolantonio 2015; Sole 2002). Poor cardiac output results in poor blood flow to other organs, can delay healing, and may set the stage for other complications. Preoperative treatment with CoQ10 can support cardiac muscle function and protect against complications (Makhija 2008; Keith 2005; de Frutos 2015).

Zinc

Zinc is a mineral that functions as an important cofactor for several enzymes involved in wound healing (Lin 2017). Adequate zinc is critical for healthy skin in general (Rostan 2002). Even those with only a mild deficiency may have poor wound healing and roughened skin (Lin 2017; Lansdown 2007; Kogan 2017). Researchers studying wound healing have found evidence that zinc is involved in every step of the process, including clotting, immune response, and the regrowth of tissue (Lin 2017; Taylor 2016).

The topical application of zinc may be beneficial to surgery patients or other patients with healing wounds (Lin 2017; Attia 2014) and venous leg ulcers (O'Connor 2014; Moreno-Eutimio 2018). Zinc supplementation improved the antioxidant status of patients recovering from burns (Berger 2007), possibly by upregulating a protein called metallothionein (Lin 2017; Rostan 2002). Animal studies showed that wound healing increases the need for zinc in the wound tissue, especially in the first few days, and zinc-dependent enzymes are critical for cell proliferation and wound healing (Kaplan 2004). Zinc administration locally, inside the bone, also improved fracture healing in rats (Krell 2017).

Melatonin

Melatonin is a hormone primarily produced in the pineal gland that affects a variety of brain functions related to sleep and wakefulness (Macchi 2004; Brown 1994). Melatonin production can be perturbed by surgery and anesthesia (Yasar 2017; Karkela 2002; Hanania 2002). It is thought that these disturbances may be correlated with certain neuropsychological changes, such as anxiety or depression, after major surgeries (Yin 2007).

Melatonin supplementation may be beneficial to surgery patients. Patients who took melatonin (1 mg per day) the night before hip surgery and for five days afterwards had better cognitive function after surgery (Fan, Yuan 2017). Similarly, patients who took melatonin the night before bariatric surgery and two hours before the procedure had better recovery, including less pain and better sleep (Ivry 2017).

During surgery, tissues are first denied sufficient oxygen when blood flow is restricted to the target area and then oxygen levels rapidly increase when blood flow is restored. This can result in oxidative stress and tissue damage. Melatonin is a free radical scavenger, which neutralizes free radicals that could otherwise damage tissues (Esteban-Zubero 2016; Mortezaee 2018). Melatonin can also reduce levels of the proinflammatory cytokine tumor necrosis factor-alpha (Esteban-Zubero 2016). Melatonin (10 to 20 mg per day) may decrease complications due to oxidative damage in patients undergoing heart surgery (Dwaich 2016; Gogenur 2014).

Curcumin

Curcumin, a major component of the spice turmeric, is a potent inhibitor of nuclear factor-kappa B, which plays a central role in the inflammatory response (Seo 2018; Shah 2017). There has been tremendous interest in inhibiting nuclear factor-kappa B to decrease the overactive inflammatory reactions in sepsis, cancer, and autoimmune diseases (Maheshwari 2006; Park 2016; Abraham 2003). Curcumin is also a powerful antioxidant (Hewlings 2017). Supplementation with curcumin (1‒1.5 grams daily) has been shown to improve markers of oxidative stress in patients with various conditions, including type 2 diabetes, osteoarthritis, and metabolic syndrome (Panahi 2017; Panahi 2016; Panahi 2015).

Alpha-Lipoic Acid

Alpha-lipoic acid is a sulfur-containing antioxidant found in spinach, broccoli, and tomatoes (Tibullo 2017; Gomes 2014; Hodges 2015). Lipoic acid can have two chemical forms, R and S. The R form is the natural form and is more readily absorbed by the body (Hermann 2014). Lipoic acid protects against oxidative stress and is essential for proper utilization of glucose in cells (Ambrosi 2018; Poh 2009).

In humans, alpha-lipoic acid may help combat free radical damage caused by high tissue concentrations of oxygen (Alleva 2005; Ambrosi 2018). In one study, 24 patients undergoing liver surgery were treated with either 600 mg alpha-lipoic acid or placebo 15 minutes before surgery began (Dunschede 2006). After surgery, blood tests for liver damage were significantly better in the alpha-lipoic acid group than in the placebo group.

Another study enrolled patients who were undergoing surgery for a simultaneous kidney and pancreas transplant (Ambrosi 2016). Surgery patients and organ donors were either untreated or treated with 600 mg alpha-lipoic acid just before surgery. After surgery, markers of inflammation and indicators of kidney damage were both decreased in the alpha-lipoic acid-treated patients.

Propolis

Propolis, a resin produced by honey bees from a variety of plant sources, has antimicrobial properties that may help heal wounds (Oryan 2018). An ointment containing propolis may help heal wounds in patients with diabetes (Afkhamizadeh 2017; Henshaw 2014). Mice supplemented orally with a propolis extract had lower levels of inflammatory cytokines and their surgical wounds closed faster (Correa 2017). Another study testing a propolis cream found similarly enhanced wound healing in rats (Iyyam Pillai 2010).

Probiotics

Probiotics are live beneficial microorganisms that improve health when used as a supplement. They keep “bad” bacteria in check. Probiotics may be particularly helpful for patients undergoing colorectal and other abdominal surgeries (Komatsu 2017; Liu, Yan 2017). In an analysis that combined data from 28 randomized clinical trials, patients undergoing gastrointestinal surgery were significantly less likely to have infections after surgery if they were taking probiotic supplements (Yang 2017). The data are particularly strong for patients taking probiotic supplements containing multiple strains (Liu, Yan 2017), but studies have not yet determined the best combinations.

N-acetyl Cysteine

N-acetyl cysteine (NAC) is a precursor of the amino acid cysteine (Sansone 2011) and the antioxidant glutathione (Ramachandran 2018; Schmitt 2015). NAC is used to prevent liver damage in patients who overdose on acetaminophen (Ramachandran 2018). NAC may help protect liver tissue from the damaging effects of reactive oxygen species during and after surgery. In one study, patients treated with NAC were less likely to have liver damage following liver surgery compared with patients who received a placebo (Donadon 2016). Another study found that patients who underwent liver surgery were less likely to have mild or severe liver failure than control patients if they received 10 grams of NAC per day intravenously, starting during surgery and continuing for three days afterwards, although the difference was not significant (Robinson 2013).

Similarly, one study found that NAC, administered for three days before surgery, may help protect the lung tissue in patients with chronic obstructive pulmonary disease undergoing coronary artery surgery (Erdil 2016). In another study conducted in 70 similar patients, half of them were treated with NAC (900 mg daily) for seven days before surgery and half were untreated. Several blood tests for kidney and liver function were significantly improved in the group receiving NAC compared with the control group (Onk 2018).

Bromelain

Bromelain is an extract from pineapple that has anti-inflammatory properties (Hale 2010; Muhammad 2017). For instance, as shown in an animal model, bromelain can inhibit signaling through tumor necrosis factor-alpha, a pro-inflammatory cytokine (Zhou 2017). Bromelain can also interact with molecules in the pain pathway (Pavan 2012). Bromelain's effects on postoperative pain have been well studied among patients undergoing wisdom tooth extraction. Although not all studies had significant results, patients treated with bromelain typically had less pain and swelling than patients treated with a control (Bormann 2016; Ghensi 2017; Majid 2014).

Beta-hydroxy beta-methylbutyrate

Beta-hydroxy beta-methylbutyrate, or HMB, is a metabolite of the amino acid leucine that can help prevent muscle wasting (Holecek 2017). Several studies have suggested that 1.5‒3 grams per day of HMB can help maintain muscle mass in patients with conditions that restrict their activity, such as those recovering from hip fractures (Malafarina 2017) and those with lung disease (Olveira 2016).

HMB may also prevent muscle wasting in patients undergoing surgery. In one study, 23 patients undergoing total knee replacement took a supplement containing HMG, arginine, and glutamine or a control for five days before and 28 days after surgery (Nishizaki 2015). Patients in the control group had a significant loss of muscle strength after surgery, but patients in the supplemented group did not.

Aloe Vera

Aloe vera, a plant that grows naturally in tropical climates and is commonly kept as a house plant, contains several bioactive phytochemicals. This plant has traditionally been used to help alleviate various skin conditions, and aloe is a common ingredient in over-the-counter skin medications and lotions (Akaberi 2016; Pereira 2016). Aloe has been found to promote wound healing by reducing inflammation and boosting collagen synthesis and blood supply (Pereira 2016).

One study specifically evaluated the effect of an aloe vera gel on surgical wounds, in this case from Cesarean sections. In 45 women, wounds were dressed with an aloe vera gel. A standard dressing was used for a control group of 45 women. After 24 hours, wound healing was significantly improved in the aloe vera group compared with the control group (Molazem 2014).

Pycnogenol

Pycnogenol is an extract from Maritime pine bark that is rich in free radical-scavenging, anti-inflammatory polyphenolic compounds (Deger 2013; Grether-Beck 2016). A growing body of evidence suggests that pycnogenol may have positive effects on skin health, improving elasticity and hydration and protecting against damage related to sun exposure (Grether-Beck 2016). In a randomized clinical trial, 30 patients with venous ulcers were treated with surgery followed by 50 mg of pycnogenol three times daily or a flavonoid combination previously shown to enhance vascular healing for 90 days. Pycnogenol was found to be as effective as the flavonoid combination at promoting healing of surgically-treated venous ulcers (Toledo 2017). Findings from another trial suggest the use of both topical and oral pycnogenol may be more effective than oral pycnogenol alone for improving healing of venous ulcers (Raffetto 2014).  Another clinical trial found that oral (systemic) and topical (local) pycnogenol preparations, alone and in combination, led to higher rates of complete healing of diabetic ulcers after six weeks of use compared with standard medications (Belcaro 2006).

In a study in rats subjected to experimental injury, the use of topical 1%, 2%, and 5% pycnogenol solutions shortened wound healing time and reduced scar size compared with pycnogenol-free solution, and the benefits were amplified as pycnogenol concentration increased (Blazso 2004). Abdominal injections of a pycnogenol solution for ten days after abdominal surgery was found to reduce adhesions better than abdominal saline injections in rats that had undergone abdominal surgery (Sahbaz 2015). Another study in rats showed that a topical pycnogenol solution reduced tissue oxidative stress and improved healing of incision wounds, and a solution made with an extract from the bark of another type of pine tree had even stronger effects (Cetin 2013).

Diabetes is well known to impair skin healing, and one animal study showed that pycnogenol may counter this problem. In the study, topical treatment with pycnogenol powder reduced the size of wounds compared with no treatment three weeks after surgical removal of small areas of skin in diabetic rats (Dogan 2017). Findings from another study in rats suggest that oral pycnogenol may reverse the negative impact of prior radiation therapy on post-surgical healing time (Deger 2013).

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