The squeez­ing cure

How 20 min­utes and a length of rope can save the life life of of a a “dummy” foal. foal.

EQUUS - - Contents - By Christine Barakat

How 20 min­utes and a length of rope can save the life of a “dummy” foal.

Wit­ness­ing the start of a foal’s life can be a pro­foundly mov­ing ex­pe­ri­ence. From ly­ing wet and shaky in the straw, to scram­bling to rise, then nick­er­ing to his dam as he nudges for his first meal, the new­born is an adorable com­bi­na­tion of vul­ner­a­bil­ity and de­ter­mi­na­tion. And in an amazingly short time---as lit­tle as 30 min­utes or at most an hour or two---he is ready to ex­plore the world, even while in­stinc­tively stick­ing close to his dam’s side. If you’ve ever been able to watch the trans­for­ma­tion in those early hours, you know it can be breath­tak­ing.

Equally pow­er­ful, in a com­pletely dif­fer­ent and heart­break­ing way, is the sight of a foal who doesn’t do well in the first hours of life. In some cases, for no clear rea­son, a young­ster seems to get “stuck” in the ear­li­est stages of the de­vel­op­men­tal timeline. He isn’t quick to rise and gain co­or­di­na­tion. He doesn’t nurse and may not even ac­knowl­edge his dam at all. He wan­ders the stall, bumps into walls and seems un­aware of his sur­round­ings. He is a “dummy foal,” the com­mon term for a con­di­tion tech­ni­cally known as neona­tal mal­ad­just­ment syn­drome (NMS).

Be­tween 3 and 5 per­cent of foals are af­fected, and all will die with­out in­ten­sive sup­port­ive treat­ment. An NMS foal needs round-the-clock care, with bot­tle-feed­ing ev­ery two hours or more fre­quently. Se­verely af­fected foals may need crit­i­cal care, in­clud­ing help reg­u­lat­ing body tem­per­a­ture. It’s an ex­haust­ing and of­ten ex­pen­sive or­deal.

When in­ten­sive care is avail­able, most NMS foals who sur­vive their first week of life make a dra­matic, sud­den im­prove­ment---lit­er­ally turn­ing around within hours---and go on to live a nor­mal, healthy life. Those who don’t im­prove are eu­tha­na­tized. And there is no way to pre­dict which cat­e­gory a dummy foal will fall into. All that could be done was wait and hope---un­til now.

John Madigan, DVM, has been treat­ing foals with NMS since he started the Uni­ver­sity of Cal­i­for­nia—Davis’ neona­tal in­ten­sive care unit in 1986.

“For a long time, ev­ery­one’s best guess was some type of hy­poxic in­jury from a trau­matic birth,” he says. “That would be a case of the foal not hav­ing enough oxy­gen at birth. But in foals so se­verely af­fected to be stag­ger­ing around their stalls, you’d ex­pect some neu­ral cell death and that they would be af­fected for life. Yet they aren’t. They re­cover com­pletely and very quickly--I’d have cases where the own­ers would tell me on a Satur­day af­ter­noon that they couldn’t con­tinue to keep the foal in in­ten­sive care at the clinic much longer. Then on Sun­day morn­ing, I’d

call them to say the foal is bounc­ing around and per­fectly fine. That doesn’t fit the hy­poxia the­ory, and that’s al­ways both­ered me.”

In the two decades since, Madigan has learned that “ev­ery­one’s best guess” is far from cor­rect.

GATH­ER­ING DIS­PARATE CLUES

Madigan be­gan to un­ravel the mys­tery of NMS in 2005, when he crashed a sci­en­tific lec­ture in New Zealand while he was on sab­bat­i­cal. “I was at a ve­teri­nary con­ven­tion when I walked into a talk on in utero lamb con­scious per­cep­tion, of all things,” he says.

The speak­ers were dis­cussing the con­scious­ness of un­born lambs in the con­text of slaugh­ter wel­fare is­sues, which wouldn’t seem to have much rel­e­vance to an equine vet­eri­nar­ian, but one small point caught Madigan’s at­ten­tion: “They were talk­ing about pro­ges­terone de­riv­a­tives act­ing as a seda­tive on the fe­tus, al­most to an anes­thetic level. Th­ese were nat­u­ral hor­mones that kept the lamb un­con­scious in utero, and there was even a com­mer­cial pro­ges­terone de­riv­a­tive avail­able to mimic that state,” he says.

Madigan’s in­ter­est was piqued be­cause of a pa­per he had read in 1992 that doc­u­mented to­tal pro­ges­terone lev­els in new­born foals: “The re­searchers found the foals had very high lev­els right af­ter birth that dropped quickly, but in two mal­ad­justed foals, those lev­els didn’t drop. They stayed high.”

Back in the lec­ture hall, the vet­eri­nar­i­ans con­tin­ued to re­fer to pro­ges­terone de­riv­a­tives that se­dated un­born lambs. “It kept com­ing up in the con­ver­sa­tion like it was a com­pletely ac­cepted and un­der­stood thing, which I guess it was among this group of sheep ex­perts,” says Madigan. “But I’d never

heard of this be­fore, and I was re­ally in­trigued. I re­mem­ber the whole room turn­ing to look at me when I started ask­ing ques­tions. I’m not sure what they thought about the Amer­i­can horse doc­tor who wan­dered into their talk and wanted to know more.”

Th­ese hor­mones, Madigan learned, keep lambs un­con­scious as they are born. “It made sense to me that foals might ex­pe­ri­ence the same thing,” he said. “You’d want a foal to be very still as it’s com­ing through the birth canal. A seda­tive neu­ro­trans­mit­ter might be at work and some­how it gets ‘switched off’ af­ter the foal is born, al­low­ing him to be­come fully con­scious and stand. But what if it didn’t switch off?”

When Madigan re­turned to Cal­i­for­nia, he asked the state rac­ing lab­o­ra­tory to cre­ate a test to quan­tify a spe­cific sub­set of pro­ges­terone lev­els in new­born foals. “I asked them for an as­say that would mea­sure neu­roseda­tive pro­ges­terones,” he says. “We ac­tu­ally started call­ing this re­search ‘The Search for the Switch.’”

Mean­while, Balazs Toth, DVM, a grad­u­ate stu­dent work­ing un­der Madigan, be­gan some re­search of his own. “We needed a short-term project and de­cided to look into the so-called ‘flop re­ac­tion’ that new­born foals have,” ex­plains Madigan.

“Any­one who has re­strained a neona­tal foal knows that if you can get your arms around their chest and hindquar­ter and hold them tight, they lit­er­ally drop, as if they are sleep­ing,” he ex­plains. “It was thought to be some form of cat­a­plexy or nar­colepsy. It hap­pens in other an­i­mals, too, and even hu­mans; any new par­ent quickly learns that swad­dling a baby tightly will help put them to sleep.”

To learn more about this phe­nom­e­non, Toth and Madigan wanted to mea­sure the brain­wave pat­terns, and sought the help of ve­teri­nary neu­rol­o­gist Mon­ica Ale­man, DVM, PhD, to do so. They also wanted to mea­sure hor­mone lev­els and other phys­i­o­log­i­cal pa­ram­e­ters of a new­born foal as he was be­ing squeezed. “The prob­lem was we couldn’t hold the squeeze long enough to col­lect enough data,” says Madigan. The so­lu­tion to that prob­lem would come from an un­ex­pected source.

“Cat­tle texts dat­ing back to the 1950s ac­tu­ally de­scribe a half-hitch rope sys­tem for putting on a calf that will cause him to flop down and lie there,” says Madigan. Toth’s study was re­designed to ap­ply the same rope tech­nique to new­born foals. “It’s im­por­tant to un­der­stand that you aren’t re­strain­ing the foal with the ropes and mak­ing it im­pos­si­ble to move,” says Madigan. “In­stead, the pres­sure from the ropes in­duces a state where he doesn’t even at­tempt to move---he al­most seems to be asleep.”

The re­searchers used the squeeze tech­nique on eight one-day-old foals, care­fully ap­ply­ing the rope, then pulling it tight. All fell to the straw in a sleepy state within min­utes and re­mained there for 20 min­utes as the gen­tle pres­sure was ap­plied. Af­ter the squeeze was re­leased, the foals perked up in a few min­utes and rose to their feet, com­pletely nor­mal. Be­fore, dur­ing and af­ter each squeeze ses­sion, re­searchers mon­i­tored the foals’ heart rates and brain waves and drew blood sam­ples for anal­y­sis.

The EEG data showed that the brain waves of the squeezed foals were con­sis­tent with sleep. The team be­gan to re­fer to the state as “squeeze-in­duced som­no­lence” or “SIS.”

The blood tests yielded more fas­ci­nat­ing data: “With squeez­ing, we saw a huge jump in foals’ hor­mone lev­els,” says Madigan. “Some peo­ple thought it was a stress re­sponse, be­cause we were han­dling them, but I had a hard time be­liev­ing that be­cause th­ese foals in no way looked stressed. They were lit­er­ally sleep­ing. In the back of my mind I kept turn­ing it over in my brain, think­ing there had to be an­other ex­pla­na­tion.”

FLIP­PING THE SWITCH

The ex­pla­na­tion Madigan was look­ing for be­gan to emerge as pieces of a larger puz­zle be­gan com­ing to­gether: “I thought about what I’d learned in New Zealand---and our search for the hor­monal switch that causes that se­dated pre-birth state. Then I con­sid­ered what we’d been ob­serv­ing in the squeeze stud­ies, which was es­sen­tially a re­turn to that state. I be­gan to won­der, what if the squeeze was the thing flip­ping that hor­monal switch?”

The more Madigan thought

Th­ese hor­mones, says John Madigan, DVM, keep lambs un­con­scious

as they are born: “It made sense to me that foals might ex­pe­ri­ence

the same thing.”

about it, the more sense it made. “As a foal trav­els through the birth canal, he’s be­ing squeezed. And that’s ex­actly the time you don’t want him mov­ing around. If the pres­sure in the birth canal was in­duc­ing this hor­mone surge, it would keep the foal quiet. Then, once he’s born and the pres­sure is re­moved, the hor­mones would get the sig­nal to drop and he’d wake up.”

In a foal with NMS, how­ever, Madigan pos­tu­lated, the mes­sage to “wake up” is never re­ceived. “Many of th­ese foals are born very, very quickly. I of­ten hear from own­ers that they went to the house for 10 min­utes and came back to find the foal. Maybe in that rush there’s a cru­cial mo­ment that doesn’t hap­pen---the mo­ment when the

hor­mones get the sig­nal to drop be­cause the foal is be­yond the birth canal. If you see th­ese foals, it is al­most as if they don’t know they were born. They are still in that sleepy, in utero state and can’t seem to snap out of it.”

What if, Madigan thought, dummy foals sim­ply never had that hor­monal switch flipped? And what if squeez­ing the foal could flip the switch man­u­ally?

The first foal Madigan was able to test his the­ory on was born at Victory Rose Farm in Va­cav­ille, Cal­i­for­nia. Over­see­ing the birth of about 70 Thor­ough­bred foals a year, owner Ellen Lee Jack­son had long re­lied on Madigan’s ser­vices on re­fer­ral by the farm vet­eri­nar­ian. She had also helped with a few of Madigan’s ear­lier re­search projects and was al­ready familiar with the squeeze tech­nique.

“We give all of our foals hy­per­im­mune plasma on their sec­ond day, just as a pre­cau­tion,” says Jack­son. “And Dr. Madigan had shown us how the squeeze tech­nique could be used to make that eas­ier, and it re­ally does. They just lie down qui­etly and let us work, so we’d been us­ing that for a while al­ready.”

Jack­son was skep­ti­cal, how­ever, when Madigan called to tell her that he thought the squeeze tech­nique might also be help­ful for dummy foals. “I was a naysayer,” she says. “Dr. Madigan is a re­ally smart guy and a cre­ative thinker, but this just seemed a lit­tle too out there, even for him.” Madigan asked if Jack­son would call him the next time a sus­pected dummy foal was born. She agreed, and it wasn’t too long af­ter­ward when a filly was born and im­me­di­ately be­gan hav­ing trou­ble.

The name of the filly is lost to both Jack­son and Madigan, but they re­mem­ber the ex­pe­ri­ence vividly. “The filly hadn’t nursed on her own and was very re­luc­tantly tak­ing a bot­tle,” says Madigan. “And when she wasn’t down, she was just bump­ing around the stall with no in­ter­est in her dam or aware­ness of where she was.” The farm vet­eri­nar­ian and staff had been sup­port­ing the filly as they would any foal with NMS and pre­par­ing them­selves and her owner for the long, ex­pen­sive and un­cer­tain road ahead.

When Madigan ar­rived at the farm, a small crowd gath­ered. “I had come down to the barn be­cause I just had to see him try this crazy idea my­self,” says Jack­son. Madigan care­fully fas­tened the rope around the filly’s chest and in a half-hitch pat­tern along her body. As he ap­plied pres­sure, she dropped to the straw as ex­pected, in a sleep-like state.

“I held the pres­sure for 20 min­utes,” says Madigan, “which is about the time a foal is nor­mally in the birth canal.” Then he re­leased the pres­sure, care­fully un­wound the ropes and stepped back to see what would hap­pen.

Within min­utes, the filly scram­bled to her feet and nick­ered to her dam. “That was the first time she’d ever nick­ered,” says Jack­son. “I couldn’t even speak I was so stunned.” The dam an­swered and the filly walked over, found her way to the ud­der and be­gan nurs­ing on her own.

“It was amaz­ing and in­cred­i­ble and ev­ery other ad­jec­tive that doesn’t seem to do it jus­tice,” says Madigan. “It was as if she’d just been born, fol­low­ing the typ­i­cal de­vel­op­men­tal timeline, with no signs of mal­ad­just­ment at all.” The ef­fects were last­ing as well; the filly de­vel­oped en­tirely nor­mally phys­i­cally and be­hav­iorally from that morn­ing on.

This meant that the squeeze of the birth canal could very well be what flips the hor­monal switch, re­leas­ing pro­ges­terone de­riv­a­tives that keep foals se­dated dur­ing birth. It also sug­gested that if that con­di­tion isn’t reversed, and the

The squeeze of the birth canal could very well be what causes the re­lease of pro­ges­terone de­riv­a­tives that keep foals se­dated dur­ing birth.

seda­tive hor­mone lev­els do not drop, a man­ual squeeze from hu­mans could repli­cate the birth process enough to re­store a nor­mal, healthy state, with no long-last­ing side ef­fects.

A fi­nal clue came not much later, with a mix­ture of hor­mones based on the rac­ing lab as­say Madigan had re­quested when he re­turned from New Zealand. “We es­sen­tially had a sy­ringe full of the pro­ges­terones that we sus­pected keep the foal se­dated through birth,” says Madigan. When he in­jected healthy foals with the hor­mones, they in­stantly went into a dummy-like state. As the hor­mone lev­els de­clined over the next few hours the foals re­turned to nor­mal. “The fact that we could in­duce the state with hor­mones, then re­verse it by al­low­ing the in­jected hor­mones to decline sug­gested the hor­mones were the cul­prit for mal­ad­just­ment syn­drome. It wasn’t just a crazy idea at that point. It seemed a valid the­ory, with sci­en­tific ev­i­dence to back it up, that was lead­ing to a real break­through in the treat­ment of th­ese foals. It doesn’t get much more ex­cit­ing than that.”

Madigan is con­tin­u­ing his re­search to learn more about the phys­i­o­log­i­cal chain of events that leads to NMS. “We still don’t know why some foals aren’t mak­ing the tran­si­tion from in­tra- to ex­trauter­ine life suc­cess­fully,” he says. “There are 35 dif­fer­ent neu­ros­teroids that could be in­volved and very spe­cific ar­eas of the brain. There’s also a pos­si­bil­ity it has to do with fe­tal cir­cu­la­tion. There’s still a lot left to in­ves­ti­gate.”

INTO THE FU­TURE

Ran­dom­ized clin­i­cal tri­als of the squeeze tech­nique are in progress, but mal­ad­justed foals can’t al­ways wait for re­search. For­tu­nately, they don’t have to: Madigan has al­ready per­son­ally used the squeeze tech­nique on 12 NMS foals

so far, and in each case, they even­tu­ally emerged from their mal­ad­justed state. “We are choos­ing the foals to do this on care­fully,” he says. “If a foal is sep­tic or truly has a hy­poxic in­jury, this isn’t go­ing to help. Those foals have other is­sues that need to be ad­dressed.”

He adds that not all NMS foals are “fixed” af­ter the first squeeze, ei­ther. “There have been some cases where we’ve had to squeeze them daily for three or four days,” he says. “They get a bit bet­ter and then revert af­ter each time. I’m not sure what is hap­pen­ing in those cases, but we are look­ing into the blood­work to see if the hor­mone lev­els bounce back up be­tween squeezes.”

In ad­di­tion to try­ing the tech­nique him­self, Madigan is spread­ing the word to other vet­eri­nar­i­ans about the po­ten­tial benefits of squeez­ing mal­ad­justed foals. He gave a three-hour pre­sen­ta­tion at the Amer­i­can As­so­ci­a­tion of Equine Prac­ti­tion­ers Con­ven­tion last De­cem­ber and he has made in­for­ma­tion avail­able to vet­eri­nar­i­ans that out­line ex­actly how to ap­ply the ropes. As a re­sult, other prac­ti­tion­ers have be­gun do­ing the tech­nique with suc­cess (see “A Let­ter of Thanks,” page 66) and shar­ing their ex­pe­ri­ences with each other. “One of my goals is for ev­ery equine vet­eri­nar­ian to know about this,” he says. “And for them to feel con­fi­dent giv­ing it a try in sus­pected cases of mal­ad­just­ment. It has the po­ten­tial to com­pletely change how we ap­proach th­ese foals.”

And while he is ex­cited about the

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