Zoobiquity

  Many physicians are only now acknowledging the link between fear and cardiovascular events. But across cultures and throughout history, this dangerous connection has been noted. Voodoo curses and overly ominous thoughts, for example, have created deadly outcomes that are hard to explain from a purely physical point of view.

  Many surgeons would sooner hang up their scrubs than operate on patients who are certain they will die on the operating table. “Surgeons are wary of people who are convinced that they will die,” Herbert Benson, a founder of the Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital told the Washington Post. Arthur Barsky, a psychiatrist at Brigham and Women’s Hospital in Boston, concurs that these patients create a “self-fulfilling prophecy.”

  It’s called the nocebo (Latin for “I will harm”) effect, the opposite of the placebo (Latin for “I will please”). Unlike the well-known effects of the placebo, a nocebo is a harmless agent that, when perceived by the patient to have malignant qualities, produces negative effects. If you’ve ever wondered whether voodoo death is real, the nocebo effect offers a reason why the answer may be yes. When the person delivering the hex is convincing enough—and the victim open-minded enough—the heart-mind connection may initiate that deadly cascade seen in stress-induced cardiac death. Some call this “homicide by heart attack.” Genetics probably plays a role, since voodoo deaths tend to cluster in specific ethnicities and regions.d

  FRADE may connect to these deaths, too. The link between folklore-laced voodoo deaths and straightforward animal capture myopathy lies in the shared biology of animal and human nervous systems.

  Over millennia, animals have developed variations—and some improvements—in the ways they can convert sensations of external danger into safety-seeking behavioral responses. Some release toxins or odors or sting with electricity or poison. Sea anemones retract when prodded and release a squirt of seawater. Flies zoom away from the swatter. But the link between threat and catecholamine release is especially pervasive and ancient. Its origins date back two billion years—before the separation of plants and animals. Potato leaves and tubers, for example, respond to stressors like cold, drought, and chemical burns by releasing catecholamines. This seems to increase the plant’s resistance to infection and other threats.

  For plants, fleeing is not an option. For vertebrates, however, a responsive heart that can accelerate in a “fleeing escape” or slow profoundly for a “hiding escape” has often meant the difference between life and death. But this elegant and effective system has a fatal flaw. Because underestimating danger even just once in a wild animal’s life can spell death, the warning system may be calibrated toward overreaction. The evolutionary medicine expert Randolph Nesse explains these overresponses through the analogy of a smoke detector. Although the alarm can sound at the wrong time, many false alarms are better than one missed true one. As the behavioral ecologists Steven Lima and Lawrence Dill wryly note, “Being killed greatly decreases future fitness.”e

  Overresponse can be found throughout biological systems. Our immune systems may “overreact” in the course of trying to protect us, causing autoimmune disorders such as rheumatoid arthritis and lupus. Eczema and keloid scar tissue are other examples of the body’s exuberant response to injury. Fevers that are possibly meant to battle microorganisms can get too high and cause seizures and brain damage. Coughing that is meant to clear vital airways can devolve into bronchospasm or cracked ribs. And in psychiatry, anxiety disorders, panic attacks, and phobias can be conceived of as pathologic overreactions to danger that stem from protective instincts.

  FRADE describes another overcalibration. Adaptively, a surge of catecholamines allows a zebra to gallop away full throttle or madly wrestle free from a lion. Maladaptively, that torrent of stress hormones may break down the animal’s muscles, destroy its kidneys, or even stop its heart. It’s counterintuitive that your brain and heart can sometimes work in concert to kill you. But FRADE is a reminder that safety systems must be powerful and can be calibrated to overrespond—especially in dangerous settings with no “do-overs.”

  Unless you’re a veterinarian, work in a pet store, or just got elected dog catcher, it’s a safe bet you don’t need to capture an animal very often. And here in the enlightened twenty-first century, we certainly don’t capture and pin down human beings all that much. Or do we?

  Once when I was on call in the ICU, a young woman was fighting for her life. A staphylococcal infection had attacked many of her organs, including her heart, which was just barely contracting and relaxing. Her kidneys had shut down and her liver was failing. The critical balance of potassium, calcium, magnesium, and sodium was dangerously disturbed. She hadn’t slept for days. A month earlier, she had been a vivacious and popular teacher at an area elementary school. But on this night, her life-threatening condition had made her disoriented … and agitated. This happens in critically ill patients so often that we have a name for it: ICU psychosis.

  Thrashing in her bed, she clawed at the nasogastric tube coming out of her left nostril. Her other hand tugged at the arterial line stuck in the soft skin of her thin left wrist. She had a Cordis line in her jugular vein, a Foley catheter in her urethra, and a hemodialysis catheter in her groin. If she pulled any of them out, blood would be everywhere. If she dislodged the intra-aortic balloon pump supporting what little blood pressure she had, she could easily rip the large, high-pressure artery and bleed to death.

  To protect her body from her volatile mind, I called for soft physical restraints. The nurses quickly and gently fastened the fleece-lined, nylon-and-cotton, six-inch-wide straps around her wrists.

  For a few seconds, all was calm. The heart monitor emitted the regular and comforting beep beep beep signifying a safe, normal rhythm.

  But then she sensed the straps on her arms. She began pulling against them. I ordered some intravenous sedation as a form of what we call “chemical restraint.” But the sick patient kept thrashing, clearly confused and quite likely terrified. And then the beeping coming from the monitor above the bed changed. It sped up and turned slightly less regular. She’d gone into VT. With her already low blood pressure, this rhythm required immediate action.

  ICU teams rehearse the lifesaving choreography these moments call for. When they happen, little needs to be said. On the left side of the patient’s chest, a nurse placed a large sticky pad the size of a paperback book connected to a wire, rolled the patient to her side, and placed another pad between her shoulder blades. My cardiology fellow dialed the knob of the defibrillator to 150 joules and calmly asked everyone to step away from the bed. The nurses and other staff members backed away, holding their hands up, palms facing out. If they touched any part of the patient or her bed, the electricity that was about to be administered would conduct into their bodies, too. The fellow pushed the raised red button marked SHOCK.

  The teacher’s body stiffened for a split second as the load of electricity coursed through her 120-pound body, which “jumped” slightly from the bed. All eyes turned to the monitor. Our ears searched for the steady beep, beep, beep. After another split second, we got it. Her cardiac rhythm snapped back to a version of normal.

  Whether she went into VT at that exact moment because of the addition of wrist restraints is impossible to say. Her acute infection had provided her with several risk factors: myocarditis, electrolyte disturbances, anemia, hypoxia. But recognizing how restraint introduces risk for cardiac arrest in animals, I now have a different perspective on how it affects human patients.

  I had always viewed physical restraint as a necessary safety intervention for my patients who required it. It’s a fixture of other professions as well—used more often than you might think. It’s common in mental health and geriatric care facilities, where modern-day straitjackets and restraints are sometimes used for patients who might be a danger to themselves or others. Law enforcement, military, and prison officers all rely on restraint devices like handcuffs to control unruly beha
vior.

  Admittedly, there are scenarios in which restraint is the best approach for the safety of all involved. I know it can be for the good of the “detainee” as well as for the cops, soldiers, prison guards, orderlies, and nurses involved, not to mention any bystanders.

  But before I learned that veterinarians view restraint as a major player in capture myopathy, I’d never even considered whether it might have a physical downside. In human medical circles, the potential risks of restraint are rarely discussed.

  Yet FRADE exists all over the animal kingdom. It’s only the separation of human and animal medicine that has allowed us to think that it doesn’t exist in human beings as well. Physicians ought to be aware of what veterinarians know: that fear, whether produced accidentally by a well-meaning doctor or purposely by a terrorist threat, can be deadly.

  As veterinarians have become more enlightened about the dangers of chase, terror, and capture, they’ve become more adamant about their responsibility to prevent capture myopathy in animals. Whether it’s a grizzly bear caught by the foot in a Canadian forest or a pet bunny on a table in a private practice, most vets agree that they can protect animals by following a few simple stress-reducing guidelines: Keep noise and motion to a minimum. Have a small, well-trained crew that can notice early signs of stress-related distress. Develop an approach that emphasizes calmness.

  Thinking about the dangers of fear and restraint has changed how I practice medicine. I still sometimes must order patients to be put in restraints, but I am cautious of the dangers and often have the vets’ guidelines in mind as I do so.

  Unraveling the threads of sudden cardiac death and capture myopathy, noticing how they twine across species, and reknitting them as FRADE led me to consider another potential danger in a quite unexpected setting. It couldn’t be farther from the watery home of an Alaskan shorebird, the back of a police car, or the hospital room of an out-of-control ICU patient. It’s the snuggly, warm cocoon of a newborn’s nursery.

  Sudden infant death syndrome (SIDS)—also known as crib death or cot death—is the leading cause of infant mortality between one month and one year of age. More than 2,500 babies die of it every year in the United States. International statistics vary, but SIDS is a leading cause of infant death in all countries in which data are available. Strictly defined, it’s “the sudden death of an infant under one year of age that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history.” The “unexplained” part is what’s so frustrating to doctors. How and why these infants silently slide from life into death in many cases goes unanswered.

  Theories abound: environmental pollution, secondhand smoke, bottle feeding, prematurity, low serotonin levels. However, so far, one factor has been overwhelmingly correlated with increased risk of SIDS: putting a baby to bed on its stomach. The reason may at first seem obvious. Too small and weak to turn itself over, an infant snuggling facedown into a soft mattress or bedding can suffocate itself. But it isn’t that simple. Babies who die of SIDS often show no postmortem evidence of asphyxiation. So examiners have asked, if these deaths weren’t respiratory, might they be cardiac?f

  When one is lying prone (facedown), the upper chambers of the heart (the atria) become full as blood rushes in from the major veins. But pressure-sensitive nerves (baroreceptors) within the atria sense the increasing volume and activate a suite of autonomic counterresponses. They decrease the urge to breathe. They also decelerate the heart. These reflexes likely share an evolutionary heritage with the ancient diving reflex, an adaptation to underwater oxygen metabolism seen in many species. And this means that putting a baby to bed on its tummy can trigger a reflexive slowing of its heart and breathing.

  The heart rates of animals as distantly related as fish and rodents also decrease, sometimes suddenly, when frightened. Loud, startling noises have been demonstrated to induce extremely slow heart rates in fawns and alligators as well as not-yet-born human infants. This heart slowing, called “fear” or “alarm” bradycardia, is a protective reflex that may keep the animal still and silent, making it less detectable to predators. And it can persist for a surprisingly long time—a minute or more. It’s especially powerful in juvenile animals and wears off somewhat as the animal matures. (For more on this, see Chapter 2, “The Feint of Heart.”)

  In the 1980s, a pathbreaking Norwegian physician with a strong knowledge of animal behavior and physiology had an early zoobiquitous moment. Birger Kaada connected the heart-slowing responses in hiding baby animals to the heart-stopping risk in sleeping baby humans. Although there was general recognition that her theory had validity, few in the medical community recognized, as she did, that some cases of SIDS could be explained by a complex overlay of two heart-slowing effects: facedown posture and fear.

  This is what might be happening in some cases. A baby is placed in the crib on its stomach, which causes a mild slowing of the heart. Then, a sudden, startling noise—a slammed door, car alarm, heated argument, telephone ring—startles and frightens the child. As with juveniles of many species, the human infant’s heart rate plummets in response to sudden jolting noises. Researchers have suggested that some infants’ immature hearts simply slow to the point of no return. Or, in other cases, the loud noise could trigger a fatal cardiac rhythm in a baby with an already slowed heart rate. In either case, this would mean that some SIDS deaths connect to the physiology of fear.

  But SIDS has another important connection to animal capture myopathy, one that suggests it’s part of FRADE. Restraint may play a lethal role in SIDS, too. But for human babies, restraint doesn’t come as a net, leg trap, or enclosure. And it doesn’t involve wrist restraints, as it does for adult psychiatric or ICU patients. Infant restraint takes the form of a centuries-old and newly revived practice: swaddling.

  Swaddling human babies is, and has been, a mainstay of parenting practices around the world. It’s said to pacify fussy infants, promote sleep, and keep babies from harming themselves—and to make it easier for caregivers to tote them around. Ideally, swaddling mimics the protective shelter of loving arms or even evokes a reassuring sense memory of a snug uterus.

  And, interestingly, swaddling offers a slight protective effect against SIDS—but only if the infant is sleeping on its back, according to a study by doctors at the Children’s University Hospital in Brussels, Belgium.

  These scientists say there’s a chilling flip side to swaddling. Put a swaddled baby to sleep on its stomach, play a sudden loud noise, and its risk for SIDS increases threefold.

  To test this, the Belgian doctors evaluated a group of infants in both swaddled and unswaddled states, their bodies positioned both prone and supine (on their backs). The babies were bound in bedsheets held in place by sandbags. (Be assured: the babies in this 2004 study were monitored constantly; the parents had given their signed consent; and a pediatrician was present the whole time.) The doctors then added a sudden “audio challenge”: three seconds of ninety-decibel white noise from a tiny speaker held about an inch from their little ears. (Ninety decibels is about as loud as a blow dryer on “high” or a motorcycle roaring by.)

  It turned out that, no matter whether sleeping on their stomachs or their backs, when “restrained” by swaddling, the babies showed earlier and more dramatic heart slowing in response to noise than the unrestrained babies. This suggests that for babies already in the dangerous facedown position, the addition of restraint in the form of swaddling might create a fatal third layer of cardiac slowing, especially with the addition of a loud, unexpected sound.

  Swaddling, it must be said, is for the most part safe, playing a role in infant care and physical and emotional security. But if swaddling joins facedown posture and startling sounds, it may be misinterpreted as predatory restraint and further slow the already decelerating heart. Pointing out the ability of noise and restraint to trigger alarm bradycardia in the young of many species adds a zoobiqu
itous piece to the SIDS puzzle. This calls for direct dialogue among animal physiologists, wildlife biologists, and the primary care pediatricians who can use this information to care for their vulnerable patients.

  Like the rhythmic beating of cardiac muscle, the conversation between the heart and the brain starts in the womb and continues until the moment we die. And thank goodness. Because sometimes being surprised, even terrified, can protect us from harm. It fuels a shorebird’s escape. It pushes a Californian to seek cover during an earthquake. Powerful yet vulnerable, the heart-brain alliance usually saves lives. But every once in a while, it can also end one.

  *Implantable cardioverter defibrillators (ICDs) are surgically placed in hearts that are at risk for arrhythmias that can lead to death. These tiny electronic devices read the heart’s rhythm 24/7. If it dangerously decelerates or accelerates, the ICD delivers twenty-five to thirty joules of electricity to “jump-start” or “pace” the heart. Patients’ descriptions of these jolts range from “heavy hiccups” to “having a donkey kick you on the chest.” Previous studies have noted increased ICD activity after emotionally charged events, including arguments.

  †Before the takotsubo designation came along, we would diagnose this syndrome as “spasm of the coronary arteries.” Certain types of people seemed prone: middle-aged women; people with histories of migraine headaches; and patients with Raynaud’s syndrome, a circulation anomaly characterized by white, blood-drained fingertips. The ill-defined heart “spasm” was also linked to cocaine use, so any patient who came into the ER with chest pain combined with suspiciously plaque-free arteries was questioned about drug habits.