Slowing the 'Cascade'

Janice Kiecolt-Glaser, PhD, is professor of psychiatry and psychology at the College of Medicine, Ohio State University, Columbus. She and husband Ronald Glaser, PhD, professor of medical microbiology and immunology, have collaborated for nearly two decades on research into the effects of stress on the immune system.

In a recent paper you outline how psychological factors may influence recovery. (6)

JKG: We studied the effects of stress on wound healing in dental students.(13) A surgeon used a surgical "punch" to make small uniform wounds on the roof of each student's mouth. One wound was made during summer vacation, and a second was made on the opposite side about six weeks later, just before exams. Stress had much larger effects on wound healing than we anticipated. The wounds took 40 percent longer on average to heal during exams than during the summer. In two other studies, one with women who cared for loved ones with Alzheimer's disease and one with mice, our research team also showed that stress can slow wound healing.(5,14)

How did the immune systems respond?

JKG: In both the human studies we measured interleukin-1b (IL-1b), a component of the immune system central to wound healing. We found that caregivers had significantly lower levels of IL-lb than non-caregivers, and that dental students produced significantly lower levels of IL-1b during exams than during vacation.

RG: IL-1b initiates a cascade of events critical to successful wound healing. It attracts cells called neutrophils and monocytes, which digest debris and bacteria at the wound site, it stimulates various components of the skin, such as fibroblasts and epithelial cells, to proliferate, and it triggers the production of other immune system components. If you look at wound healing as a cascade, and stress limits the very early part of that cascade, then it's not surprising that stress slows down the process.

What about other psychological factors - such as pain - that might affect recovery?

JKG: Pain may affect recovery through several different paths. Certainly, pain has been used in animal experiments as a stressor to increase stress hormones and modulate immune function. People will sleep poorly if they're in pain, and the stress hormones that result from sleeping poorly will not help healing. Also, people who are in pain may smoke more or use alcohol to try to deal with the pain. So, in a variety of ways, pain could serve as a central gateway after surgery to poorer healing over time.

What about things like smoking and alcohol? Do they affect how our bodies react to surgery?

JKG: Absolutely. Nicotine and other chemicals in smoke have a number of adverse effects on wound healing. Some cosmetic surgeons are reluctant to operate on smokers because of the much poorer healing. Alcohol use can also cause a number of problems with surgery.

What other factors might affect recovery?

RG: One of the obvious ones is age. The older people are, the more difficult it is for them to recover from surgery. Age is associated with poorer immune function, and unfortunately, the majority of surgeries are among older adults. So the very folks that need to heal most rapidly are those who, because of age, may heal more slowly.

What do you do if you're somebody facing surgery?

JKG: Based on the literature, it appears that it matters a lot how distressed people are going into surgery. Most people are going to be anxious going into it. It's unrealistic to think that you wouldn't be. But there are obvious things you can do. Don't work up until the last minute so you are not frantic when you actually go into surgery. Try to get the information that will help you feel better. For some people that may be a lot more information than for other people. And it is probably quite important to feel comfortable with the surgeon about what's going to happen.

What we might consider really trivial interventions, psychologically, have very significant consequences. Even very brief contact between patient and surgeon appears to be remarkably helpful. Most interventions last half an hour and much of that is often done through videotapes or in groups, so it doesn't need to be personalized. Even something as simple as giving patients a pamphlet appears to have effects, as does placing patients in a hospital room with a view.

In one study, patients who were recovering from gallbladder surgery spent significantly less time in the hospital and used fewer pain medications when their hospital room looked out on a wooded courtyard compared to those whose view was a brick wall.(21)

RG: Within the context of managed health care, there are relatively inexpensive, simple interventions that don't cost much, but can potentially reduce hospital stays, reduce the risk of infections and other complications, and speed recovery. When you multiply that by the number of people getting surgery, you're talking about saving a lot of money.

Interview:

Learning from Roommates

James A. Kulik, PhD, professor of psychology at the University of California at San Diego, has studied psychological interventions to improve recovery from surgery for more than 15 years.

Q. You've found that educational videotapes can speed recovery from heart bypass surgery.(12)

A. We had patients watch one of three videotapes in addition to the hospital's usual preparation, then compared them to patients who got only the usual preparation. All of the tapes featured a nurse-expert as narrator. Two of the videotapes included interviews with patients before and after the procedure. In one of these tapes, the basic tone was that recovery would be a steady progression. The other tape had a bit more emphasis on possible complications.

It turned out that patients who saw any of the tapes spent significantly less time in the intensive care unit following the operation and significantly less time in the hospital than did those who got just the standard preparation. There were no significant differences among the groups who watched different tapes.

Q. What other effects did the tapes have?

A. The patients who saw the videotapes felt better prepared for the surgery, at least psychologically. But that didn't explain why they recovered more quickly. What really mattered was that they had more confidence that they would be able to do various things after surgery that would be important for their recovery, such as deep breathing exercises and getting up and walking even when they didn't feel like it.

We have a similar study underway looking at recovery in the longer term. The only preliminary thing I can say is that the patient tapes again are showing benefits. The message is that patients do benefit from knowing what to expect and what to do - being active participants in the recovery as opposed to passive recipients.

Q. How important is social support from spouses and others?

A. A lot of epidemiological evidence shows that people who are married are less likely to have heart attacks and other heart-related problems. Our results, however, suggest that being married in and of itself does not necessarily confer an advantage to by-pass surgery patients in terms of how fast they recover in the hospital.(10) Rather, married patients who receive frequent visits in the hospital do better than married patients who don't.

So we see evidence that spousal support can actually shorten the length of hospital stay and improve the well-being of the patient. In the longer term, it can also improve compliance with recommended lifestyle changes, such as diet and exercise, and probably longer-term health, though that's a little less documented.(9)

Q. What evidence have you seen of that?

A. Look closely at the large-scale, nicotine gum and patch studies that have been done over the past 10 or 15 years. Women do worse than men in virtually every study. Sometimes there is not a significant difference because the sample sizes are too small, but when you look across them all, this trend always is present. One report concluded that a year after the largest nicotine patch study, 31 percent of the men were still not smoking, as opposed to 22 percent of the women.

Q. You also looked at pairing heart patients with different roommates.(8) Tell us about that.

A. In that work, some bypass patients had a roommate, some did not. In some cases the roommate was a fellow bypass patient, sometimes he was not. Finally, sometimes the roommate was post-operative and sometimes he was not. We found that being in the same room with a fellow heart patient improved recovery. If your roommate had already been through an operation, there was an additional benefit. Those with a post-op bypass roommate did best.

At least two possible mechanisms are at work. One is an information model: you learn more from a fellow cardiac patient than somebody who's not a cardiac patient. If your roommate is post-operative instead of pre-operative, you also learn things like the need to get up and walk. Separate from that is the idea that there's support - more of an emotional dimension, if you will - that can be picked up from fellow patients. Our evidence on that is not quite as strong, but that doesn't mean it isn't happening.

Q. Let's say I'm about to have heart surgery. My hospital doesn't offer me a videotape, and my roommate is awaiting a hernia repair. What advice would you give me?

A. Ask the nurses if there is somebody on the floor who has been through this recently who might be willing to talk with you. From our roommate work, we don't know exactly how long an exposure is necessary to get the benefit. It could be that talking to somebody for an hour is sufficient, or that you really do need to spend more time with the person.

The Power of Positive Thinking

Thinking positively has profound effects on the physical and mental health of surgery patients, says Michael F. Scheier, PhD, of Carnegie Mellon University. Scheier and his colleagues have found that optimists who have heart bypass surgery recover and return to their usual activities more quickly and are less likely to be hospitalized again for complications than are their pessimistic peers.

When the researchers followed bypass patients' recovery, they found that those who scored high on a 10-item "optimism" questionnaire Scheier developed and evaluated in previous research recovered more quickly and were more likely to resume normal activities during the first six months after surgery. Five years after surgery, they were more likely to have taken steps to prevent further problems: they changed their diets, took aspirin daily, and enrolled in a cardiac rehabilitation program.18,19 In more recent work, Scheier's team tracked more than 300 bypass patients following surgery and found that optimists were less likely to be hospitalized again for reasons related to the surgery or their heart disease.(17)

Scheier believes it would be difficult to change a pessimist's worldview directly, and that "a better tack might be to try to alter some of the behaviors and coping styles that distinguish them from optimists." Pessimists, for example, are more likely to use denial as a coping strategy, which not only prevents them from confronting the reality of the situation, it also prevents them from taking steps to improve their lives.

"If you can get pessimists to alter the concrete things they are doing, they may ultimately feel better and do better, and in that backdoor kind of way, change their expectations and their orientation to the world," he says.

Cost-Cutting

Evidence suggests that low-cost behavioral efforts can cut away post-surgery dollars that are now spent on hospitalization. The research, although scant, is compelling.

For example, in a 1989 study at the University of Southern Mississippi, 40 children about to undergo surgery watched one of two videos - one narrated by a child and the other by an adult - depicting what happens before, during, and after surgery. Total cost was $30.83 per child.

Compared to 20 children who did not see the videos, those who did reported less pain, got up and moved about sooner, and were discharged sooner, resulting in an average net saving of $214 per child- equivalent to a half-day or more in the hospital. (16)

'Feeling' the Pain Even When You Don't

Having your body cut open while you're awake is, to say the least, quite stressful. Ample evidence now exists, however, that even when it happens under general anesthesia, the body knows it is being assaulted and reacts in ways that can have grave consequences for your health.

The key, it appears, is to keep the pain from reaching the brain and triggering the stress responses.

One research team found that patients undergoing colon surgery who received general anesthesia had higher levels of stress hormones afterwards and lower levels of tumor-fighting natural killer (NK) cells than did patients who received epidural anesthesia - which blocks pain sensations from reaching the brain. (7)

Another team found that patients who received general anesthesia during abdominal surgery had a higher stress response and significantly more infectious, cardiac, and respiratory complications than did those given epidural anesthesia. (22)

Gayle G. Page, DNSc, of Johns Hopkins University, has been using rats to study the effects of surgical pain on the spread of breast cancer.(15) Most recently, she and her colleagues anesthetized and operated on four groups of rats: some who received additional pain medicine before the procedure, some who got it afterwards, some who got it both times, and some who received none.

All the rats were injected with a strain of breast cancer cells known to metastasize to the lungs. Rats that received pain medication had fewer tumors in their lungs than those that did not, and those that received the medication before the procedure showed the fewest new tumors.

Surgery normally leads to a drop in NK cells, Page explains. Her results suggest that pain medication can prevent this decrease in NK cell activity, leaving the rats better able to fight off the cancer. It is as yet unknown whether pain medications have similar effects in people with cancer.

Painful Expectations

One of the earliest attempts to improve surgical recovery with a psychological intervention was conducted in the early 1960s by Lawrence D. Egbert, MD, at the Massachusetts General Hospital.(4)

Egbert, an anesthesiologist, and his colleagues visited 97 patients the night before they were to have abdominal surgery. Each patient was told how he or she would be prepared for anesthesia and how long the surgery would last. About half also were told about the nature and severity of pain they would feel afterward and received instructions on relaxing their stomach muscles, taking deep breaths, and other techniques to minimize the pain.

In the days immediately after surgery, those who had been briefed about pain used only half the amount of narcotic painkillers as those who were not briefed, Egbert and his colleagues reported. Patients briefed about pain also went home 2.7 days sooner on average.

The Research

1. Abbott J and Abbott P (1995) "Psychological and Cardiovascular Predictors of Anaesthesia Induction, Operative and Post-Operative Complications in Minor Gynaecological Surgery," British Journal of Clinical Psychology, 34:613-623.
2. Czeisler, CA et al. (1976) "Episodic 24-Hour Cortisol Secretory Patterns in Patients Awaiting Elective Cardiac Surgery," Journal of Clinical Endocrinology and Metabolism, 42:273-283.
3. de Groot, KI et al. (1997) "The Influence of Psychological Variables on Postoperative Anxiety and Physical Complaints in Patients Undergoing Lumbar Surgery," Pain, 69:19-25.
4. Egbert, LD. (1964) "Reduction of Postoperative Pain by Encouragement and Instruction of Patients," NEJM, 270:825-827.
5. Kiecolt-Glaser, JK, Marucha, PT, et al. (1995) "Slowing of Wound Healing by Psychological Stress," Lancet, 346:1194-1196.
6. Kiecolt-Glaser, JK, Page GG, et al. (1998) "Psychological Influences on Surgical Recovery: Perspectives from Psychoneuroimmunology," American Psychologist, 53: 1209-1218.
7. Koltun, WA et al. (1996) "Awake Epidural Anesthesia Is Associated With Improved Natural Killer Cell Cytotoxicity and a Reduced Stress Response," American Journal of Surgery, 171:68-73.
8. Kulik, JA, Mahler, HIM, et al. (1996) "Social Comparison and Affiliation Under Threat: Effects on Recovery from Major Surgery," Journal of Personality and Social Psychology, 71:967-979.
9. Kulik, JA and Mahler, HIM. (1993) "Emotional Support as a Moderator of Adjustment and Compliance After Coronary Artery Bypass Surgery: A Longitudinal Study," Journal of Behavioral Medicine, 16:45-63.
10. Kulik, JA and Mahler, HIM. (1989) "Social Support and Recovery from Surgery," Health Psychology, 8:221-238.
11. Liu, R et al. (1994) "Effects of Background Stress and Anxiety on Postoperative Recovery," Anaesthesia, 49:382-386.
12. Mahler, HIM, and Kulik, JA. (1998) "Effects of Preparatory Videotapes on Self-Efficacy Beliefs and Recovery from Coronary Bypass Surgery," Annals of Behavioral Medicine, 20:39-46.
13. Marucha, PT, Kiecolt-Glaser, JK, et al. (1998) "Mucosal Wound Healing is Impaired by Examination Stress," Psychosomatic Medicine, 60:362-365.
14. Padgett, DA, Marucha, PT, et al. (1998) "Restraint Stress Slows Cutaneous Wound Healing in Mice," Brain, Behavior, and Immunity, 8:241-250.
15. Page, GG et al. (1998) "Preoperative Versus Postoperative Administration of Morphine: Impact on the Neuroendocrine, Behavioural, and Metastatic-Enhancing Effects of Surgery," British Journal of Anesthesia, 81:216-223.
16. Pinto, RP and Hollandsworth, JG (1989) "Using Videotape Modeling to Prepare Children Psychologically for Surgery: Influence of Parents and Costs Versus Benefits of Providing Preparation Services," Health Psychology, 8:79-95. (Contact: 317 338-6094)
17. Scheier, MF et al. (In Press) "Optimism and Rehospitalization Following Coronary Artery Bypass Graft Surgery," Archives of Internal Medicine.
18. Scheier, MF et al. (1989) "Dispositional Optimism and Recovery from Coronary Artery Bypass Surgery: The Beneficial Effects on Physical and Psychological Well-Being," Journal of Personality and Social Psychology, 57:1024-1040.
19. Scheier, MF and Carver, CS. (1992) "Effects of Optimism on Psychological and Physical Well-Being: Theoretical Overview and Empirical Update," Cognitive Therapy and Research, 16:201-228.
20. Tusek, DL et al. (1997) "Guided Imagery: A Significant Advance in the Care of Patients Undergoing Elective Colorectal Surgery," Diseases of the Colon and Rectum, 40:172-178.
21. Ulrich, RS. (1984) "View Through a Window May Influence Recovery from Surgery," Science, 224:420-421.
22. Yeager, MP. (1987) "Epidural Anesthesia and Analgesia in High-Risk Surgical Patients," Anesthesiology, 66:729-736.

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