Guest guest Posted September 27, 1999 Report Share Posted September 27, 1999 >As for online medical articles, compliments of our Canadian friends, Connie > & Kistler (Hi Guys!) see " Special Problems Of Anesthesia For Little >People " , written by Dr. Judith Hall. See URL: >http://www.bfree.on.ca/comdir/family/lpo/INDEX.HTM#INDEX From someone who has been under the anaesthetic a few times, my thanks for this info are belated, but gratefully given. I've printed it off for hopefully, NOT future reference. However, it IS frightening what some of us have risked, out of shear ignorance, in past operations. Thanks again Fred Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 12, 2002 Report Share Posted January 12, 2002 > My son is going to have surgery on his arm in 2 weeks. He has repeatedly > dislocated it and suffered a wrestling injury with it last week. He is 17. > He can not have gluten, casein, milk, eggs, rice, soy, red dye. Does anyone > have any advice? The gluten free web sites say our kids can't have dextrose. > Isn't that what is in the IV? They can use either dextrose or saline. (sugar or salt). >Any advice would be greatly appreciated. Be IN the OR or right outside with the surgeon having agreed what to do and how to do it aware you are checking up on him. These guys tend to do what they want to once they are behind closed doors. Get your instructions for him in the chart and have him sign off on them. Remember to have each member of the surgical team sign off, and review them with you. > > ellen V. Little > Wellness and Marketing Consultant > mvlittle@a... > www.5pillars.com/813399000 > Toll Free 1-866-215-3966 > (716) 634-1771 Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 9, 2003 Report Share Posted January 9, 2003 I am one who NEVER has had stomach problems. Never eaten a TUMS, or taken pepto-bismol, don't know what heartburn is... But in all 3 surgeries (c-toma, breast lump, and endometriosis - just call me " tumor lady " ), I have had vomiting each time. Even though I tell the anesthesiologist and I am given anti-nausea meds, I still barf big time EVERY TIME. I absolutely hate it. I think the last srugery, we discovered it was probably the morphine they gave me post-op that was making me continue to throw up. I am told that I should ask for the motion sickness patch next time. You have to apply it at least 4 hours before surgery for it to be effective. If someone tries this, pleaselet us know if it works. Sandi > Just chiming in here...I think Candy's prep for the worst/hope for the best motto sounds about right. I had no nausea with surgeries 1 & 3, some with #2, & wicked nausea after #4. I'm sure there's a reason, but it seems almost random. > > If you have a history of nausea, TELL the anesthesiologist. He (or she) will be speaking with you before surgery, asking you questions. Don't be shy - that's the time to let them know about nausea, anxiety, etc., so they can adjust/be ready. They gave me anti-nausea & anti-anxiety stuff before going into the OR, & then put anti- nausea stuff in my IV in recovery (I'm sure they were doing it during the op, but I was wherever one goes under anesthesia!). > > Yes, you do stink a bit for a couple of days. Funny smell, funny taste. It passes. > > One last thing, for needle-phobics - they can give you a little shot in the back of your hand before they insert the IV needle. It does burn/sting for a few moments, then numbs everything so for the IV insertion you feel nothing. If you have no trouble with IVs going in you may not need the little shot (the nurse says she uses it about 50% of the time) but it's an option. > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 22, 2004 Report Share Posted February 22, 2004 Kathy, I had wanted epidural with " conscious sedation " and the " amnesia drug. " As it turned out, on the advice of the anesthesologist and for various reasons, I had the epidural and a general anesthesia. He asked me what I was most scared of. I told him, feeling nauseous and being sick afterwards. He said I have three anti-nausea drugs, each one is 80% effective. I'll give you all three. I was did not have one second of nausea! Also, as some of you know, I am a big proponent of SmartWater and I am sure that drinking tons of water with those electrolytes after I got home cleared out any anesthesia " fog brain " in record time. I would say, don't be afraid to express any fears when the anesthesologist comes to talk to you before surgery. They don't want you to be miserable. Except for one brief moment at the end of surgery, I don't remember anything from the time they wheeled me out of pre-op until I got to my room on the ortho floor. > Hi all this is Kathy again the 38 year old scheduled for RTHR on > April 9th. A year and a half ago I under went Laproscopic surgery to > remove a torn labrum while in for that they did abrasion (drilled > holes in my hip joint to regenerate a fibro cartilage)this procedure > was in hopes that it would buy me 5 years before the THR. Here I am > no time bought heading in for yet another sugery. Well my biggest > fear is the anesthesia not from dying from it but from how sick I > was from it the last time (wished I was dead). I read a few posts > about the epidural approach and being awake for the surgery this > intrigues me. First of all I am a big chicken! So the thought of > being aware of anything makes me think I am better off with general > anesthisia and to just deal with the sickness. Your thoughts and > honest opinions are appreciated anyone that has undergone this > surgery could you please share your experiences. > > I also want to once again thank everyone that is part of this board. > All of the experiences shared has greatly helped me mentally prepare > for this surgery. I am less frightened today that I was when I first > posted. Thanks! Kathy Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 22, 2004 Report Share Posted February 22, 2004 Many people have epidural anesthesia for hip replacement surgery. They don't necessarily remember everything because they are also given heavy sedation along with the epidural. As to your concerns with nausea in conjunction with general anesthesia, if you tell the anesthetist or anesthesiologist that you've had a problem with that in the past you can be given medicine that will help. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 23, 2004 Report Share Posted February 23, 2004 I just had my thr on the 16th and went with an epidural with a seditive. Trust me it's much easier! Kenny > > Hi all this is Kathy again the 38 year old scheduled for RTHR on > > April 9th. A year and a half ago I under went Laproscopic surgery > to > > remove a torn labrum while in for that they did abrasion (drilled > > holes in my hip joint to regenerate a fibro cartilage)this > procedure > > was in hopes that it would buy me 5 years before the THR. Here I am > > no time bought heading in for yet another sugery. Well my biggest > > fear is the anesthesia not from dying from it but from how sick I > > was from it the last time (wished I was dead). I read a few posts > > about the epidural approach and being awake for the surgery this > > intrigues me. First of all I am a big chicken! So the thought of > > being aware of anything makes me think I am better off with general > > anesthisia and to just deal with the sickness. Your thoughts and > > honest opinions are appreciated anyone that has undergone this > > surgery could you please share your experiences. > > > > I also want to once again thank everyone that is part of this > board. > > All of the experiences shared has greatly helped me mentally > prepare > > for this surgery. I am less frightened today that I was when I > first > > posted. Thanks! Kathy Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 23, 2004 Report Share Posted February 23, 2004 Hi Kathy, I was told by my surgeon that he would definitely use the epidural, but also said that you're not going to be totally awake, he described it to me as more of a twilight sleep. I won't know for sure until I go, I'm a week before you, on april 1st. I'll let you know. - :-) > Hi all this is Kathy again the 38 year old scheduled for RTHR on > April 9th. A year and a half ago I under went Laproscopic surgery to > remove a torn labrum while in for that they did abrasion (drilled > holes in my hip joint to regenerate a fibro cartilage)this procedure > was in hopes that it would buy me 5 years before the THR. Here I am > no time bought heading in for yet another sugery. Well my biggest > fear is the anesthesia not from dying from it but from how sick I > was from it the last time (wished I was dead). I read a few posts > about the epidural approach and being awake for the surgery this > intrigues me. First of all I am a big chicken! So the thought of > being aware of anything makes me think I am better off with general > anesthisia and to just deal with the sickness. Your thoughts and > honest opinions are appreciated anyone that has undergone this > surgery could you please share your experiences. > > I also want to once again thank everyone that is part of this board. > All of the experiences shared has greatly helped me mentally prepare > for this surgery. I am less frightened today that I was when I first > posted. Thanks! Kathy Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 18, 2004 Report Share Posted March 18, 2004 The ARI website has info re: anesthesia with autistic kids. We took a copy of it to our gastroenterologist when had his gastroscopy...I don't know if he did anything different, though. We will be praying for your friend's daughter, their family and docs. , mom to and Anesthesia > Dear list mates, > A little of the subject matter, but I was hoping for help because I can not > find in archives. I remember some postings a while back regarding a child's > reactions to anesthesia and there was a parent that had talked to the > anesthesiologist and come to some sort of solution. Could someone please > advise as there is a friend of ours that needs to have their (ASD dx) > daughter under while a brain tumor is removed. They are of course terrified, > but that said the one time she had anesthesia that she regressed terribly > for several months before they could get her back. Any advise will be > appreciated. > Shery > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 22, 2004 Report Share Posted March 22, 2004 I'm not promoting this idea, but wanted to through it out to be investigated. Lately I've been doing a lot of research on the uses of vitamin C. One of the things I recall reading is it's supposed incredible benefit of bringing one out quicker after being through anestisia. The DAN! doctor I am seeing for this had been a surgeon and personally would swear by it's benefits. Thinking there must be something to it, because if you are going to get novacane they don't want you taking vitamin C for 24 hours prior because it will not be as effective. Kari Anesthesia Dear list mates, A little of the subject matter, but I was hoping for help because I can not find in archives. I remember some postings a while back regarding a child's reactions to anesthesia and there was a parent that had talked to the anesthesiologist and come to some sort of solution. Could someone please advise as there is a friend of ours that needs to have their (ASD dx) daughter under while a brain tumor is removed. They are of course terrified, but that said the one time she had anesthesia that she regressed terribly for several months before they could get her back. Any advise will be appreciated. Shery Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 23, 2004 Report Share Posted March 23, 2004 People with B12 pathway problems have problems with anesthesia. Migfht be worth checking into. anesthesia > Halleluia!!! > > Finally, I have found someone with similar problems... My son first got his diagnosis (PDD-NOS) after having 2 surgeries a week apart. The second one lasted about 6 hours. Last year he had surgery again to have his tonsils removed... BINGO, another behavioral regression!!!!! > > I have tried to search the archives too, but have not found it. If anyone can give me any references on this, I do appreciate it!!! > > Coral > > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 23, 2004 Report Share Posted March 23, 2004 Last Nov our son was going to have tonsils and adenoids removed. We found out anesthesia is soy based, which he is allergic to. We cancelled the surgery. Hospital got into some hot water. They give a lot of different meds. Are you having another surgery? I do have some suggestions of you are. anesthesia Halleluia!!! Finally, I have found someone with similar problems... My son first got his diagnosis (PDD-NOS) after having 2 surgeries a week apart. The second one lasted about 6 hours. Last year he had surgery again to have his tonsils removed... BINGO, another behavioral regression!!!!! I have tried to search the archives too, but have not found it. If anyone can give me any references on this, I do appreciate it!!! Coral Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 23, 2004 Report Share Posted March 23, 2004 They are wanting to set up another one-so would love some suggestions for them! anesthesia Halleluia!!! Finally, I have found someone with similar problems... My son first got his diagnosis (PDD-NOS) after having 2 surgeries a week apart. The second one lasted about 6 hours. Last year he had surgery again to have his tonsils removed... BINGO, another behavioral regression!!!!! I have tried to search the archives too, but have not found it. If anyone can give me any references on this, I do appreciate it!!! Coral Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 23, 2004 Report Share Posted March 23, 2004 What kind of surgery are we talking about? Suggestions: 1st- Set up an appointment with the anesthesiologist ASAP. Get your doctor on board with whatever allergies and complications exist. Have him send a letter to the " group " or a specific anesthesiologist if you can get one. 2nd- Have the surgery done at a childrens hospital that deals with complicated issues. 3rd- Becareful of Tylenol. What they use has dye in it. Find out if you can get a substitute. They were crabby with me on this one- the rest tend to thin the blood. 4th- Get the records of what meds were administered in the other surgery's and REQUIRE the doc to review the file and find replacements for meds that might have caused a reaction. - Of coarse, make sure you document/remember the reactions that happened before. 5th- Call the hospital pharmacy and tell them you need the formulation (containing everything in the stuff) of all the materials the doctor listed plus all the iv vehicles. 6th- Check on the bags that hold meds for surgery. Sounds strange, but its actually well documented how they leach chemicals. The pharmacist was well aware of this issue when I asked, and he said they had replaced them with a new vendor- and newly designed bags. Hospitals used to use glass only. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 24, 2004 Report Share Posted March 24, 2004 Thanks for all the suggestions!!!! Coral Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 24, 2004 Report Share Posted March 24, 2004 Hello , Not all anaesthetic agents are soy based. Were you meaning propofol? Usually it can be substituted with another when there is a problem if allergies/sensitivities are indicated. Sorry you had to cancel. Regards, Joe Quote Link to comment Share on other sites More sharing options...
Guest guest Posted March 24, 2004 Report Share Posted March 24, 2004 Yes, I believe that was the one. I probably sounded as if I was generalizing to all agents... That tends to happen to me on the net.. I basically have no trust in medical professionals and triple check everything they do now. In our case, my son had a skin prick allergy to soy, so I cant imagine what they could have done to him. I shudder to think.... Now, I think if I had to have surgery for him, I would demand an anestesiologist that had a speciality for complications (even though he has never had a problem because he has never had surgery). I would be in the funny farm if they screwed him up again. Their general attitude toward me was laughable- like I shouldn't question the meds they were giving, shouldn't ask for the ingredients, or double check the procedure. In the end, I didn't make a stink about the huge mistake they 'almost made'. The guy wouldn't even give me a definative list of meds - he said any doc might do the surgery depending on the rotation, and they all have their own 'recipes'. When I discovered it on the internet after demanding all the names of meds they " might use " - (as he would not provide me a list from the pharmacy) - I cancelled the surgery (the day before). This guy was so stupid, he called and left a message on my machine saying " Don't worry, I checked with the pharmacy and all the ingredients you say he's reactive to arent there " . It was pathetic incompetance. I guess I havent gotten over it yet. RE: anesthesia Hello , Not all anaesthetic agents are soy based. Were you meaning propofol? Usually it can be substituted with another when there is a problem if allergies/sensitivities are indicated. Sorry you had to cancel. Regards, Joe Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 23, 2004 Report Share Posted September 23, 2004 i am a nurse anesthetist and I found this article on the internet. My child is on the spectrum and we are going to have MTHFR testing done. Currently I am taking folic acid for a high homocystine level( MTHFR defect). I have heard that they think this gene has something to do with folate metabolism which our kids need for metal metabolism. I have been practicing for over 20 years and when we put kids to sleep we use high flows of nitrous. Last year I started getting numbness in my face and arms. I had a cat scan and they found nothing wrong. But then I discovered I got the numbness after I did a room full of kids that day. Still trying to figure that one out but I am now trying not to do as many kids if possible. Pass this to your anesthesia friend....Sym ---------- HOME | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | HELP ---------- You are signed in as symc at Registered Visitor level | Sign Out | Edit Your Information ---------- ---------- ---------- Previous Volume 349:45-50 ---------- July 3, 2003 ---------- Number 1 Next ---------- Adverse Effect of Nitrous Oxide in a Child with 5,10-Methylenetetrahydrofolate Reductase Deficiency R. Selzer, Ph.D., S. Rosenblatt, M.D., Renata Laxova, M.D., and Kirk Hogan, M.D., J.D. ---------- ---------- ---------- ---------- PDF ---------- PDA Full Text ---------- Supplementary Material ---------- ---------- ---------- ---------- Perspective ---------- by Erbe, R. W. ---------- Letters ---------- ---------- ---------- ---------- Add to Personal Archive ---------- Add to Citation Manager ---------- Notify a Friend ---------- E-mail When Cited ---------- E-mail When Letters Appear ---------- ---------- ---------- ---------- Find Similar Articles ---------- PubMed Citation ---------- Nitrous oxide irreversibly oxidizes the cobalt atom of vitamin B12, thereby inhibiting the activity of the cobalamin-dependent enzyme methionine synthase (or 5-methyltetrahydrofolate–homocysteine S-methyltransferase; Enzyme Commission code EC 2.1.1.13). Methionine synthase catalyzes the remethylation of 5-methyltetrahydrofolate and homocysteine to tetrahydrofolate and methionine (Figure 1). Methionine, by way of its activated form, S-adenosylmethionine, is the principal substrate for methylation in many biochemical reactions, including assembly of the myelin sheath, methyl substitutions in neurotransmitters, and DNA synthesis in rapidly proliferating tissues.1 ---------- View larger version (13K): [in this window] [in a new window] Figure 1. The Folate and Homocysteine Metabolic Cycles and the Enzymatic Site of Nitrous Oxide Toxicity. Co denotes cobalt. We report the neurologic deterioration and death of a child anesthetized twice with nitrous oxide before the diagnosis of 5,10-methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) deficiency (Online Mendelian Inheritance in Man number 236250) was established.2 MTHFR catalyzes the synthesis of 5-methyltetrahydrofolate. Sequence analysis of RNA transcripts and genomic DNA from the patient and his family members, together with direct assays of MTHFR activity in fibroblasts, revealed that the enzyme deficiency was caused by a novel MTHFR mutation (1755G ---------- A), which changes the conserved methionine at position 581 of the enzyme to isoleucine; this mutation is coinherited with two other, common MTHFR polymorphisms (677C ---------- T and 1298A ---------- C), each of which is associated with depressed enzyme function.3,4 We propose that a nitrous oxide–induced defect of methionine synthase superimposed on an inherited defect of MTHFR caused the patient's death. Case Report Details of the patient's clinical course and biochemical and pathological findings were reported by Beckman et al. in 1987.2 In brief, the child appeared normal until three months of age, when a mass in the left leg was noted. It was not known before the patient's surgery that his father and one of his uncles had serum levels of total homocysteine above 20.0 µmol per liter and above 30.0 µmol per liter, respectively (normal range, 5.4 to 13.9). The proband's sibling, who was receiving lifelong therapy with high-dose vitamin B supplements, had a homocysteine level of 4.3 µmol per liter. Neither the father nor the sibling had received nitrous oxide. On preoperative assessment for excisional biopsy of the mass, the patient's physical status was deemed class I according to the American Society of Anesthesiologists criteria (class I denotes good health and class V critical illness). After premedication with atropine and induction of anesthesia with sodium thiopental and succinylcholine, the child's trachea was intubated; anesthesia was maintained with 0.75 percent halothane and 60 percent nitrous oxide in oxygen for 45 minutes. The surgical biopsy revealed an infantile fibrosarcoma, and resection of the mass was performed on the fourth day after the biopsy. After induction of anesthesia with halothane, the child was anesthetized for 270 minutes with 0.75 percent halothane and 60 percent nitrous oxide. At the conclusion of the operation, his trachea was extubated, and he was transferred while awake to the intensive care unit. He was discharged on the seventh postoperative day in apparently good health. Seventeen days later (25 days after the resection), the patient was admitted because of seizures and episodes of apnea. On examination, the infant was severely hypotonic, without reflexes and with ataxic ventilation. Cranial computed tomography showed generalized atrophy of the brain, with enlarged prepontine and medullary cisterns. The urine was positive for homocystine (1.30 µmol per milligram of creatinine [normal value, 0]) but negative for organic acids and methylmalonic acid. The plasma homocystine level was elevated, at 0.6 mg per deciliter (normal value, <0.01), and the methionine level was low, at 0.06 mg per deciliter (normal mean [±SD] value, 0.48±0.18); the vitamin B12 level was normal, at 403 pg per milliliter (297 pmol per liter) (normal range, 150 to 800 pg per milliliter [111 to 590 pmol per liter]). The serum folate level, measured by radioimmunoassay, was 3.8 ng per milliliter (8.5 nmol per liter) (normal range, 2.5 to 15.0 ng per milliliter [5.6 to 33.4 nmol per liter]), and the level of folate in the cerebrospinal fluid was 26.0 ng per milliliter (57.9 nmol per liter) (normal range, 10.6 to 85.0 ng per milliliter [23.6 to 189.2 nmol per liter]). The patient died at 130 days of age (46 days after the resection) after a respiratory arrest. An autopsy showed asymmetric cerebral atrophy and severe demyelination, with astrogliosis and oligodendroglial-c ell depletion in the midbrain, medulla, and cerebellum. The values for MTHFR activity in cultured fibroblasts reported post mortem were 1.22 and 0.8 nmol of formaldehyde produced per milligram of protein per hour (normal mean value, 5.04±1.36) with and without flavinadenine dinucleotide, respectively. The simultaneous control values were 6.4 and 5.4 nmol of formaldehyde produced per hour per milligram of protein with and without flavinadenine dinucleotide, respectively.5 Methods The investigations were carried out with approval of the University of Wisconsin's institutional review board. Written informed consent was obtained from all the participants. Fibroblast Culture and MTHFR Activity Fibroblasts were cultured from skin-punch biopsy specimens obtained from both parents and from the patient's stored samples. MTHFR activity was measured at confluence, as previously described.6 All the assays were performed in duplicate, with simultaneous assay of a normal control. Preparation and Sequence Analysis of Genomic DNA Genomic DNA was isolated from the cultured fibroblasts from the patient and both parents and from either blood or buccal cells from other relatives. Each of the 11 MTHFR exons was amplified from genomic DNA by the polymerase chain reaction (PCR) with the use of newly designed intronic primers.7,8 (The sequences of the primers are listed in Supplementary Appendix 1 with the full text of this article at http://www.nejm.org.) The patient's and both parents' PCR products were bidirectionally sequenced. A novel mutation in the patient's DNA at nucleotide 1755 (exon 10) and two previously described frequent polymorphisms at positions 677 (exon 4) and 1298 (exon 7) in the MTHFR gene were analyzed in the genomic DNA from the parents and other relatives with the use of the restriction enzymes NlaIII, HinfI, and MboII, as previously described.3,4 Family members were also screened as previously described for common polymorphisms in the genes encoding enzymes that regulate folate and homocysteine metabolism; these polymorphisms have been implicated in the pathogenesis of neural-tube defects, other congenital anomalies, and cardiovascular and neoplastic disease.9 The polymorphisms include those that encode methionine synthase (MTR; the polymorphism results in the substitution of glycine for aspartic acid at residue 919),10 methionine synthase reductase (MTRR; the polymorphism results in the substitution of methionine for isoleucine at residue 22),11 and cystathionine ---------- -synthase (CBS; the polymorphism is a 68-bp duplication).12 RNA Analysis To evaluate the expression of an intact copy of the predominant 7.2-kb MTHFR isoform,13 RNA was isolated from the patient's cultured fibroblasts. A 2206-bp product containing the entire coding region was amplified by PCR from the complementary DNA (cDNA) transcript and sequenced in full. The 7.2-kb cDNA product was amplified as seven overlapping fragments ranging from 1.0 to 2.2 kb in size, as verified by gel electrophoresis. (The primers used to sequence the cDNA transcript and to amplify the cDNA as overlapping fragments are listed in Supplementary Appendixes 2 and 3, respectively, with the full text of this article at http://www.nejm.org.) Bands corresponding to the expected fragment sizes were excised, and the first 300 bases of the 5' and 3' ends were sequenced to allow positive identification of each fragment. Fragments from the patient and an unrelated control were then compared. Results Enzyme Activity in Fibroblasts The patient's MTHFR activity in two replicates was 0.76 and 0.03 nmol of formaldehyde per milligram of protein per hour (normal mean value, 13.3±4.6 with the use of the current method of measurement6), with a simultaneous normal control of 11.52 nmol of formaldehyde per milligram of protein per hour. MTHFR activity in the father and mother (1.8 and 6.1 nmol of formaldehyde per milligram of protein per hour, respectively) was reduced, with a control level of 9.5 nmol of formaldehyde per milligram of protein per hour. Genomic DNA-Sequence Analysis The patient was found to be heterozygous for a novel mutation, 1755G ---------- A in exon 10, which causes a substitution of isoleucine for methionine at residue 581 (M581I)14 (GenBank accession number, NM_005957). Restriction-enzyme analysis confirmed the presence of the 1755G ---------- A mutation in the heterozygous patient, his father, his brother, one uncle, and one aunt, but not in 100 control chromosomes. The patient was also heterozygous for a 677C ---------- T mutation in exon 4 (resulting in a substitution of valine for alanine at residue 222) and a 1298A ---------- C mutation in exon 7 (resulting in a substitution of alanine for glutamic acid at residue 429). In addition to being heterozygous for 1755G ---------- A, the father was homozygous (TT) for the 677C ---------- T mutation and homozygous (AA) at 1298A (Figure 2). The mother was heterozygous for both common polymorphisms and homozygous (wild type) at 1755G. The sibling's haplotype was identical to that of the patient in all coding regions. The novel mutation at 1755G ---------- A was therefore transmitted to the patient from a paternal chromosome, in cis configuration with the 677C ---------- T mutation. Two of the father's four siblings had haplotypes identical to the father's haplotype and were heterozygous for the 1755G ---------- A mutation and homozygous for the 677C ---------- T mutation (Table 1). ---------- View larger version (6K): [in this window] [in a new window] Figure 2. Nucleotide Changes in the MTHFR Gene in the Patient and His Parents. In addition to the coding changes, the patient (the proband) and his mother were heterozygous for a substitution of adenine for cysteine at position 2355, which is 375 bases (in the 3' direction) from the stop codon, on the same chromosome as the 1298C polymorphism. This substitution is in a region of unknown importance. Asterisks denote DNA-sequence variants. The open bars represent the MTHFR gene, and the black bars the remainder of each chromosome in the pair. View this table: [in this window] [in a new window] Table 1. Polymorphisms in the Patient and Members of His Family. We sequenced 25 to 40 bases beyond all intronic boundaries to look for altered splice junctions. There were no substitutions in the 5' and 3' untranslated regions flanking the MTHFR gene, within or proximate to a putative binding site for a transcription factor or an actual start site mapped by Gaughan et al.13 and Homberger et al.15 The DNA sequence approximately 550 bp in the 3' direction from the MTHFR stop codon and a 400-bp segment encompassing the distal 3'-polyadenylation site contained several polymorphisms, but none at sites with recognized functional significance. We also performed genomic analysis of the genes encoding methionine synthase, methionine synthase reductase, and cystathionine ---------- -synthase. Genotypes at these loci for all members of the pedigree are provided in Table 1. RNA Analysis No size differences were observed among the seven MTHFR cDNA fragments, indicating that the patient's fibroblasts expressed an intact MTHFR transcript. The 2.2-kb product contained the entire coding region of the transcript and was used to sequence a region beginning 50 bp in the 5' direction from the translational start site and ending 150 bp downstream of the stop codon. This product was of the expected length, and no alternate splicing variants were detected. The entire product was sequenced and compared with the published sequence14 (GenBank accession number, NM_005957). The presence of the heterozygous common polymorphisms 677C ---------- T and 1298A ---------- C, as well as the heterozygote substitution 1775G ---------- A, was confirmed. Discussion The inactivation of methionine synthase by nitrous oxide has been demonstrated with purified enzyme,16 in cultured cells,17,18 in animal models,19 and in humans.20,21,22 The mean half-time of inactivation is 46 minutes. Residual methionine synthase activity more than 200 minutes after the start of nitrous oxide administration approaches zero.21 Mice, pigs, and rats exposed to nitrous oxide have delayed recovery of enzyme activity for periods of four days or more.19,23,24,25 Recovery in cultured cells indicates that nitrous oxide–mediated inhibition is irreversible, with de novo synthesis of the enzyme required to restore activity.26 The untoward consequences of nitrous oxide anesthesia in our patient are reminiscent of two recent case reports. In the first, an eight-month-old child had acute neurologic deterioration six days after an 80-minute period of anesthesia with nitrous oxide.27 In the second, a four-month-old child was admitted because of hypotonia, dehydration, and acidosis three weeks after surgery that had involved a 180-minute period of anesthesia with nitrous oxide.28 Both children were found to have severe dietary cobalamin deficiency. These instances of methionine synthase inhibition have a time course and clinical features similar to those observed in our patient but were nonlethal, perhaps because they were elicited after only a single exposure to nitrous oxide. Moreover, our patient had an inborn error of metabolism in an essential precursor in a metabolic pathway, rather than an acquired deficiency, and nitrous oxide was delivered on two occasions only a few days apart. Severe MTHFR deficiency is an autosomal recessive disorder characterized by progressive hypotonia, convulsions, and psychomotor retardation. The clinical presentation may be subtle, with the disorder manifested as developmental disability in the setting of moderate homocystinuria and hyperhomocysteinemia and low-to-normal levels of plasma methionine.29 Twenty-nine mutations in MTHFR are associated with severe deficiency, with a resulting activity level that is usually 0 to 30 percent of control activity.7,8,14,30,31,32,33 Most patients are heterozygous for multiple MTHFR substitutions; a small minority are homozygous for mutations at this locus. The 1755G ---------- A substitution identified in our patient occurs in a phylogenetically conserved region of the MTHFR protein (as assessed with BLASTP software, version 2.2.1). This region, which is thought to be essential for functional protein folding,34 is a " hot spot " for mutations leading to MTHFR deficiency (1711C ---------- T, 1727C ---------- T, 1762A ---------- T, and 1768G ---------- A).7,8 The heterozygous presence of the 1755G ---------- A substitution in the patient's father, brother, one uncle, and one aunt and its absence in 100 independent control chromosomes suggest that it is not a benign variant. Compound heterozygosity for the common MTHFR alleles 677C ---------- T and 1298A ---------- C, as seen in the patient, his mother, and his brother, causes elevations in the plasma homocysteine level4 that are associated with a 50 to 60 percent decrement in enzyme activity.35 In the absence of coding mutations elsewhere in the MTHFR gene or evidence of a mutant splice variant, our patient's deficient enzyme activity may be attributable to compound heterozygosity for the novel 1755G ---------- A mutation, with the prevalent 677C ---------- T polymorphism on the same (paternal) chromosome and the 1298A ---------- C mutation on the maternal chromosome. It has recently been shown that when mutations causing severe MTHFR deficiency are expressed in cis configuration with the common 677C ---------- T variant, the resultant phenotype is markedly aggravated.34 Every year, approximately 45 million persons in North America undergo anesthesia, and nitrous oxide constitutes a major component in about half these procedures.36 Because of the growing use of nitrous oxide,37,38,39,40,41 patients with known mutations associated with mild or severe abnormalities in folate-cycle enzymes are increasingly likely to receive nitrous oxide. On the strength of the current findings, we believe that patients with a diagnosis of severe MTHFR deficiency should not receive nitrous oxide as anesthesia. In the case of emergency procedures, patients whose clinical presentation fits that of severe MTHFR deficiency, even if the disorder has not been diagnosed, should also not receive nitrous oxide. In the case of elective procedures, patients whose clinical presentation fits that of severe MTHFR deficiency should be evaluated, and the diagnosis should be ruled out before anesthesia with nitrous oxide is contemplated. Supported by grants from the Doris Duke Foundation and the University of Wisconsin Department of Anesthesiology Research and Development Fund (to Dr. Hogan) and the Canadian Institutes of Health Research (to Dr. Rosenblatt). We are indebted to Singh Sekhon, Ph.D. (University of Wisconsin, Madison), for the fibroblast cultures and to H. , M.D. (Metabolite Laboratories, Denver), for the assays of total homocysteine. Source Information From the Departments of Anesthesiology (R.R.S., K.H.) and Medical Genetics (R.L.), University of Wisconsin Medical School, Madison; and the Departments of Human Genetics, Medicine, Pediatrics, and Biology, McGill University, Montreal (D.S.R.). Address reprint requests to Dr. Hogan at the Department of Anesthesiology, B6/319 Clinical Sciences Center, 600 Highland Ave., Madison, WI 53792, or at khogan@.... References 1. Chiang PK, Gordon RK, Tal J, et al. S-adenosylmethionine and methylation. FASEB J 1996;10:471-480.[Abstract] 2. Beckman DR, Hoganson G, Berlow S, Gilbert EF. Pathological findings in 5,10-methylene tetrahydrofolate reductase deficiency. Birth Defects Orig Artic Ser 1987;23:47-64.[Medline] 3. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-113.[iSI][Medline] 4. van der Put NM, Gabreels F, s EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 1998;62:1044-1051.[CrossRef][iSI][Medline] 5. Kanwar YS, Manaligod JR, Wong PW. Morphologic studies in a patient with homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. Pediatr Res 1976;10:598-609.[Abstract] 6. Rosenblatt DS, Erbe RW. Methylenetetrahydrofolate reductase in cultured human cells. I. Growth and metabolic studies. Pediatr Res 1977;11:1137-1141.[iSI][Medline] 7. Sibani S, Christensen B, O'Ferrall E, et al. Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat 2000;15:280-287.[CrossRef][iSI][Medline] 8. Kluijtmans LA, Wendel U, s EM, van den Heuvel LP, Trijbels FJ, Blom HJ. Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. Eur J Hum Genet 1998;6:257-265.[CrossRef][iSI][Medline] 9. Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics 2001;1:189-201. 10. Harmon DL, Shields DC, Woodside JV, et al. Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations. Genet Epidemiol 1999;17:298-309.[CrossRef][iSI][Medline] 11. A, Platt R, Wu Q, et al. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab 1999;67:317-323.[CrossRef][iSI][Medline] 12. Tsai MY, Bignell M, Schwichtenberg K, Hanson NQ. High prevalence of a mutation in the cystathionine beta-synthase gene. Am J Hum Genet 1996;59:1262-1267.[iSI][Medline] 13. Gaughan DJ, Barbaux S, Kluijtmans LA, Whitehead AS. The human and mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic organization, mRNA structure and linkage to the CLCN6 gene. Gene 2000;257:279-289.[CrossRef][iSI][Medline] 14. Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet 1994;7:551-551. 15. Homberger A, Linnebank M, Winter C, et al. Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene. Eur J Hum Genet 2000;8:725-729.[CrossRef][iSI][Medline] 16. Frasca V, Riazzi BS, s RG. In vitro inactivation of methionine synthase by nitrous oxide. J Biol Chem 1986;261:15823-15826.[Abstract/Full Text] 17. Christensen B, Rosenblatt DS, Chu RC, Ueland PM. Effect of methionine and nitrous oxide on homocysteine export and remethylation in fibroblasts from cystathionine synthase-deficient, cblG, and cblE patients. Pediatr Res 1994;35:3-9.[Abstract] 18. Fiskerstrand T, Ueland PM, Refsum H. Folate depletion induced by methotrexate affects methionine synthase activity and its susceptibility to inactivation by nitrous oxide. J Pharmacol Exp Ther 1997;282:1305-1311.[Abstract/Full Text] 19. Kondo H, Osborne ML, Kolhouse JF, et al. Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats. J Clin Invest 1981;67:1270-1283.[iSI][Medline] 20. Koblin DD, Waskell L, JE, Stokstad EL, Eger EI II. Nitrous oxide inactivates methionine synthetase in human liver. Anesth Analg 1982;61:75-78.[Abstract] 21. Royston BD, Nunn JF, Weinbren HK, Royston D, Cormack RS. Rate of inactivation of human and rodent hepatic methionine synthase by nitrous oxide. Anesthesiology 1988;68:213-216.[iSI][Medline] 22. Christensen B, Guttormsen AB, Schneede J, et al. Preoperative methionine loading enhances restoration of the cobalamin-dependent enzyme methionine synthase after nitrous oxide anesthesia. Anesthesiology 1994;80:1046-1056.[iSI][Medline] 23. Deacon R, Lumb M, J, et al. Inactivation of methionine synthase by nitrous oxide. Eur J Biochem 1980;104:419-423.[Abstract] 24. Molloy AM, Orsi B, Kennedy DG, Kennedy S, Weir DG, JM. The relationship between the activity of methionine synthase and the ratio of S-adenosylmethionine to S-adenosylhomocysteine in the brain and other tissues of the pig. Biochem Pharmacol 1992;44:1349-1355.[CrossRef][iSI][Medline] 25. Koblin DD, JE, Deady JE, Stokstad EL, Eger EI II. Inactivation of methionine synthetase by nitrous oxide in mice. Anesthesiology 1981;54:318-324.[iSI][Medline] 26. Riedel B, Fiskerstrand T, Refsum H, Ueland PM. Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase. Biochem J 1999;341:133-138.[CrossRef][iSI][Medline] 27. Felmet K, Robins B, Tilford D, Hayflick SJ. Acute neurologic decompensation in an infant with cobalamin deficiency exposed to nitrous oxide. J Pediatr 2000;137:427-428.[CrossRef][iSI][Medline] 28. McNeely JK, Buczulinski B, Rosner DR. Severe neurological impairment in an infant after nitrous oxide anesthesia. Anesthesiology 2000;93:1549-1550.[iSI][Medline] 29. Rosenblatt DS, Fenton WA. Inherited disorders of folate and cobalamin transport and metabolism. In: Scriber CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic & molecular bases of inherited disease. 8th ed. Vol. 3. New York: McGraw-Hill, 2001:3897-933. 30. Goyette P, Christensen B, Rosenblatt DS, Rozen R. Severe and mild mutations in cis for the methyelentetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. Am J Hum Genet 1996;59:1268-1275.[iSI][Medline] 31. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 1995;56:1052-1059.[iSI][Medline] 32. Tonetti C, Amiel J, Munnich A, Zittoun J. Impact of new mutations in the methylenetetrahydrofolate reductase gene assessed on biochemical phenotypes: a familial study. J Inherit Metab Dis 2001;24:833-842.[CrossRef][iSI][Medline] 33. Homberger A, Linnebank M, Sewell A, Suormala T, Fowler B, Koch HG. Severe methylenetetrahydrofolate reductase deficiency: two novel genotypes with different clinical course. J Inherit Metab Dis 2001;24:Suppl 1:50-50. abstract. 34. Goyette P, Rozen R. The thermolabile variant 677C ---------- T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase. Hum Mutat 2000;16:132-138.[iSI][Medline] 35. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998;64:169-172.[CrossRef][iSI][Medline] 36. Orkin FK, SJ. Scope of modern anesthetic practice. In: RD, ed. Anesthesia. 5th ed. Vol. 2. Philadelphia: Churchill Livingstone, 2000:2577-85. 37. Peretz B, Katz J, Zilburg I, Shemer J. Response to nitrous-oxide and oxygen among dental phobic patients. Int Dent J 1998;48:17-23.[iSI][Medline] 38. Keating HJ III, Kundrat M. Patient-controlled analgesia with nitrous oxide in cancer pain. J Pain Symptom Manage 1996;11:126-130.[CrossRef][iSI][Medline] 39. Luhmann JD, Kennedy RM, Porter FL, JP, Jaffe DM. A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. Ann Emerg Med 2001;37:20-27.[CrossRef][iSI][Medline] 40. Castera L, Negre I, Samii K, Buffet C. Patient-administered nitrous oxide/oxygen inhalation provides safe and effective analgesia for percutaneous liver biopsy: a randomized placebo-controlled trial. Am J Gastroenterol 2001;96:1553-1557.[CrossRef][iSI][Medline] 41. Krauss B. Continuous-flow nitrous oxide: searching for the ideal procedural anxiolytic for toddlers. Ann Emerg Med 2001;37:61-62.[CrossRef][iSI][Medline] ---------- ---------- ---------- ---------- PDF ---------- PDA Full Text ---------- Supplementary Material ---------- ---------- ---------- ---------- Perspective ---------- by Erbe, R. W. ---------- Letters ---------- ---------- ---------- ---------- Add to Personal Archive ---------- Add to Citation Manager ---------- Notify a Friend ---------- E-mail When Cited ---------- E-mail When Letters Appear ---------- ---------- ---------- ---------- Find Similar Articles ---------- PubMed Citation ---------- Related Letters: Nitrous Oxide and 5,10-Methylenetetrahydrofolate Reductase Burman J. F., Kaufman J. L., Hogan K., Erbe R. W. Extract | Full Text | PDF N Engl J Med 2003; 349:1479-1480, Oct 9, 2003. Correspondence This article has been cited by other articles: • (2003). Lucina. Arch. Dis. Child. 88: 1142-1142 [Full Text] • (2003). Fatal Combination: Nitrous Oxide Anesthesia and Methionine Pathway Defects. Journal Watch Neurology 2003: 5-5 [Full Text] • Burman, J. F., Kaufman, J. L., Hogan, K., Erbe, R. W. (2003). Nitrous Oxide and 5,10-Methylenetetrahydrofolate Reductase. N Engl J Med 349: 1479-1480 [Full Text] HOME | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | HELP Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2004 Massachusetts Medical Society. All rights reserved. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 24, 2004 Report Share Posted September 24, 2004 Pardon me for asking, but if your experiencing these symptoms from the possibility of nitrous and putting kids to sleep ..... what effect does that have on the children? That kind of scares me. Shauna [ ] Re: anesthesia i am a nurse anesthetist and I found this article on the internet. My child is on the spectrum and we are going to have MTHFR testing done. Currently I am taking folic acid for a high homocystine level( MTHFR defect). I have heard that they think this gene has something to do with folate metabolism which our kids need for metal metabolism. I have been practicing for over 20 years and when we put kids to sleep we use high flows of nitrous. Last year I started getting numbness in my face and arms. I had a cat scan and they found nothing wrong. But then I discovered I got the numbness after I did a room full of kids that day. Still trying to figure that one out but I am now trying not to do as many kids if possible. Pass this to your anesthesia friend....Sym ---------- HOME | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | HELP ---------- You are signed in as symc at Registered Visitor level | Sign Out | Edit Your Information ---------- ---------- ---------- Previous Volume 349:45-50 ---------- July 3, 2003 ---------- Number 1 Next ---------- Adverse Effect of Nitrous Oxide in a Child with 5,10-Methylenetetrahydrofolate Reductase Deficiency R. Selzer, Ph.D., S. Rosenblatt, M.D., Renata Laxova, M.D., and Kirk Hogan, M.D., J.D. ---------- ---------- ---------- ---------- PDF ---------- PDA Full Text ---------- Supplementary Material ---------- ---------- ---------- ---------- Perspective ---------- by Erbe, R. W. ---------- Letters ---------- ---------- ---------- ---------- Add to Personal Archive ---------- Add to Citation Manager ---------- Notify a Friend ---------- E-mail When Cited ---------- E-mail When Letters Appear ---------- ---------- ---------- ---------- Find Similar Articles ---------- PubMed Citation ---------- Nitrous oxide irreversibly oxidizes the cobalt atom of vitamin B12, thereby inhibiting the activity of the cobalamin-dependent enzyme methionine synthase (or 5-methyltetrahydrofolate-homocysteine S-methyltransferase; Enzyme Commission code EC 2.1.1.13). Methionine synthase catalyzes the remethylation of 5-methyltetrahydrofolate and homocysteine to tetrahydrofolate and methionine (Figure 1). Methionine, by way of its activated form, S-adenosylmethionine, is the principal substrate for methylation in many biochemical reactions, including assembly of the myelin sheath, methyl substitutions in neurotransmitters, and DNA synthesis in rapidly proliferating tissues.1 ---------- View larger version (13K): [in this window] [in a new window] Figure 1. The Folate and Homocysteine Metabolic Cycles and the Enzymatic Site of Nitrous Oxide Toxicity. Co denotes cobalt. We report the neurologic deterioration and death of a child anesthetized twice with nitrous oxide before the diagnosis of 5,10-methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) deficiency (Online Mendelian Inheritance in Man number 236250) was established.2 MTHFR catalyzes the synthesis of 5-methyltetrahydrofolate. Sequence analysis of RNA transcripts and genomic DNA from the patient and his family members, together with direct assays of MTHFR activity in fibroblasts, revealed that the enzyme deficiency was caused by a novel MTHFR mutation (1755G ---------- A), which changes the conserved methionine at position 581 of the enzyme to isoleucine; this mutation is coinherited with two other, common MTHFR polymorphisms (677C ---------- T and 1298A ---------- C), each of which is associated with depressed enzyme function.3,4 We propose that a nitrous oxide-induced defect of methionine synthase superimposed on an inherited defect of MTHFR caused the patient's death. Case Report Details of the patient's clinical course and biochemical and pathological findings were reported by Beckman et al. in 1987.2 In brief, the child appeared normal until three months of age, when a mass in the left leg was noted. It was not known before the patient's surgery that his father and one of his uncles had serum levels of total homocysteine above 20.0 µmol per liter and above 30.0 µmol per liter, respectively (normal range, 5.4 to 13.9). The proband's sibling, who was receiving lifelong therapy with high-dose vitamin B supplements, had a homocysteine level of 4.3 µmol per liter. Neither the father nor the sibling had received nitrous oxide. On preoperative assessment for excisional biopsy of the mass, the patient's physical status was deemed class I according to the American Society of Anesthesiologists criteria (class I denotes good health and class V critical illness). After premedication with atropine and induction of anesthesia with sodium thiopental and succinylcholine, the child's trachea was intubated; anesthesia was maintained with 0.75 percent halothane and 60 percent nitrous oxide in oxygen for 45 minutes. The surgical biopsy revealed an infantile fibrosarcoma, and resection of the mass was performed on the fourth day after the biopsy. After induction of anesthesia with halothane, the child was anesthetized for 270 minutes with 0.75 percent halothane and 60 percent nitrous oxide. At the conclusion of the operation, his trachea was extubated, and he was transferred while awake to the intensive care unit. He was discharged on the seventh postoperative day in apparently good health. Seventeen days later (25 days after the resection), the patient was admitted because of seizures and episodes of apnea. On examination, the infant was severely hypotonic, without reflexes and with ataxic ventilation. Cranial computed tomography showed generalized atrophy of the brain, with enlarged prepontine and medullary cisterns. The urine was positive for homocystine (1.30 µmol per milligram of creatinine [normal value, 0]) but negative for organic acids and methylmalonic acid. The plasma homocystine level was elevated, at 0.6 mg per deciliter (normal value, <0.01), and the methionine level was low, at 0.06 mg per deciliter (normal mean [±SD] value, 0.48±0.18); the vitamin B12 level was normal, at 403 pg per milliliter (297 pmol per liter) (normal range, 150 to 800 pg per milliliter [111 to 590 pmol per liter]). The serum folate level, measured by radioimmunoassay, was 3.8 ng per milliliter (8.5 nmol per liter) (normal range, 2.5 to 15.0 ng per milliliter [5.6 to 33.4 nmol per liter]), and the level of folate in the cerebrospinal fluid was 26.0 ng per milliliter (57.9 nmol per liter) (normal range, 10.6 to 85.0 ng per milliliter [23.6 to 189.2 nmol per liter]). The patient died at 130 days of age (46 days after the resection) after a respiratory arrest. An autopsy showed asymmetric cerebral atrophy and severe demyelination, with astrogliosis and oligodendroglial-c ell depletion in the midbrain, medulla, and cerebellum. The values for MTHFR activity in cultured fibroblasts reported post mortem were 1.22 and 0.8 nmol of formaldehyde produced per milligram of protein per hour (normal mean value, 5.04±1.36) with and without flavinadenine dinucleotide, respectively. The simultaneous control values were 6.4 and 5.4 nmol of formaldehyde produced per hour per milligram of protein with and without flavinadenine dinucleotide, respectively.5 Methods The investigations were carried out with approval of the University of Wisconsin's institutional review board. Written informed consent was obtained from all the participants. Fibroblast Culture and MTHFR Activity Fibroblasts were cultured from skin-punch biopsy specimens obtained from both parents and from the patient's stored samples. MTHFR activity was measured at confluence, as previously described.6 All the assays were performed in duplicate, with simultaneous assay of a normal control. Preparation and Sequence Analysis of Genomic DNA Genomic DNA was isolated from the cultured fibroblasts from the patient and both parents and from either blood or buccal cells from other relatives. Each of the 11 MTHFR exons was amplified from genomic DNA by the polymerase chain reaction (PCR) with the use of newly designed intronic primers.7,8 (The sequences of the primers are listed in Supplementary Appendix 1 with the full text of this article at http://www.nejm.org.) The patient's and both parents' PCR products were bidirectionally sequenced. A novel mutation in the patient's DNA at nucleotide 1755 (exon 10) and two previously described frequent polymorphisms at positions 677 (exon 4) and 1298 (exon 7) in the MTHFR gene were analyzed in the genomic DNA from the parents and other relatives with the use of the restriction enzymes NlaIII, HinfI, and MboII, as previously described.3,4 Family members were also screened as previously described for common polymorphisms in the genes encoding enzymes that regulate folate and homocysteine metabolism; these polymorphisms have been implicated in the pathogenesis of neural-tube defects, other congenital anomalies, and cardiovascular and neoplastic disease.9 The polymorphisms include those that encode methionine synthase (MTR; the polymorphism results in the substitution of glycine for aspartic acid at residue 919),10 methionine synthase reductase (MTRR; the polymorphism results in the substitution of methionine for isoleucine at residue 22),11 and cystathionine ---------- -synthase (CBS; the polymorphism is a 68-bp duplication).12 RNA Analysis To evaluate the expression of an intact copy of the predominant 7.2-kb MTHFR isoform,13 RNA was isolated from the patient's cultured fibroblasts. A 2206-bp product containing the entire coding region was amplified by PCR from the complementary DNA (cDNA) transcript and sequenced in full. The 7.2-kb cDNA product was amplified as seven overlapping fragments ranging from 1.0 to 2.2 kb in size, as verified by gel electrophoresis. (The primers used to sequence the cDNA transcript and to amplify the cDNA as overlapping fragments are listed in Supplementary Appendixes 2 and 3, respectively, with the full text of this article at http://www.nejm.org.) Bands corresponding to the expected fragment sizes were excised, and the first 300 bases of the 5' and 3' ends were sequenced to allow positive identification of each fragment. Fragments from the patient and an unrelated control were then compared. Results Enzyme Activity in Fibroblasts The patient's MTHFR activity in two replicates was 0.76 and 0.03 nmol of formaldehyde per milligram of protein per hour (normal mean value, 13.3±4.6 with the use of the current method of measurement6), with a simultaneous normal control of 11.52 nmol of formaldehyde per milligram of protein per hour. MTHFR activity in the father and mother (1.8 and 6.1 nmol of formaldehyde per milligram of protein per hour, respectively) was reduced, with a control level of 9.5 nmol of formaldehyde per milligram of protein per hour. Genomic DNA-Sequence Analysis The patient was found to be heterozygous for a novel mutation, 1755G ---------- A in exon 10, which causes a substitution of isoleucine for methionine at residue 581 (M581I)14 (GenBank accession number, NM_005957). Restriction-enzyme analysis confirmed the presence of the 1755G ---------- A mutation in the heterozygous patient, his father, his brother, one uncle, and one aunt, but not in 100 control chromosomes. The patient was also heterozygous for a 677C ---------- T mutation in exon 4 (resulting in a substitution of valine for alanine at residue 222) and a 1298A ---------- C mutation in exon 7 (resulting in a substitution of alanine for glutamic acid at residue 429). In addition to being heterozygous for 1755G ---------- A, the father was homozygous (TT) for the 677C ---------- T mutation and homozygous (AA) at 1298A (Figure 2). The mother was heterozygous for both common polymorphisms and homozygous (wild type) at 1755G. The sibling's haplotype was identical to that of the patient in all coding regions. The novel mutation at 1755G ---------- A was therefore transmitted to the patient from a paternal chromosome, in cis configuration with the 677C ---------- T mutation. Two of the father's four siblings had haplotypes identical to the father's haplotype and were heterozygous for the 1755G ---------- A mutation and homozygous for the 677C ---------- T mutation (Table 1). ---------- View larger version (6K): [in this window] [in a new window] Figure 2. Nucleotide Changes in the MTHFR Gene in the Patient and His Parents. In addition to the coding changes, the patient (the proband) and his mother were heterozygous for a substitution of adenine for cysteine at position 2355, which is 375 bases (in the 3' direction) from the stop codon, on the same chromosome as the 1298C polymorphism. This substitution is in a region of unknown importance. Asterisks denote DNA-sequence variants. The open bars represent the MTHFR gene, and the black bars the remainder of each chromosome in the pair. View this table: [in this window] [in a new window] Table 1. Polymorphisms in the Patient and Members of His Family. We sequenced 25 to 40 bases beyond all intronic boundaries to look for altered splice junctions. There were no substitutions in the 5' and 3' untranslated regions flanking the MTHFR gene, within or proximate to a putative binding site for a transcription factor or an actual start site mapped by Gaughan et al.13 and Homberger et al.15 The DNA sequence approximately 550 bp in the 3' direction from the MTHFR stop codon and a 400-bp segment encompassing the distal 3'-polyadenylation site contained several polymorphisms, but none at sites with recognized functional significance. We also performed genomic analysis of the genes encoding methionine synthase, methionine synthase reductase, and cystathionine ---------- -synthase. Genotypes at these loci for all members of the pedigree are provided in Table 1. RNA Analysis No size differences were observed among the seven MTHFR cDNA fragments, indicating that the patient's fibroblasts expressed an intact MTHFR transcript. The 2.2-kb product contained the entire coding region of the transcript and was used to sequence a region beginning 50 bp in the 5' direction from the translational start site and ending 150 bp downstream of the stop codon. This product was of the expected length, and no alternate splicing variants were detected. The entire product was sequenced and compared with the published sequence14 (GenBank accession number, NM_005957). The presence of the heterozygous common polymorphisms 677C ---------- T and 1298A ---------- C, as well as the heterozygote substitution 1775G ---------- A, was confirmed. Discussion The inactivation of methionine synthase by nitrous oxide has been demonstrated with purified enzyme,16 in cultured cells,17,18 in animal models,19 and in humans.20,21,22 The mean half-time of inactivation is 46 minutes. Residual methionine synthase activity more than 200 minutes after the start of nitrous oxide administration approaches zero.21 Mice, pigs, and rats exposed to nitrous oxide have delayed recovery of enzyme activity for periods of four days or more.19,23,24,25 Recovery in cultured cells indicates that nitrous oxide-mediated inhibition is irreversible, with de novo synthesis of the enzyme required to restore activity.26 The untoward consequences of nitrous oxide anesthesia in our patient are reminiscent of two recent case reports. In the first, an eight-month-old child had acute neurologic deterioration six days after an 80-minute period of anesthesia with nitrous oxide.27 In the second, a four-month-old child was admitted because of hypotonia, dehydration, and acidosis three weeks after surgery that had involved a 180-minute period of anesthesia with nitrous oxide.28 Both children were found to have severe dietary cobalamin deficiency. These instances of methionine synthase inhibition have a time course and clinical features similar to those observed in our patient but were nonlethal, perhaps because they were elicited after only a single exposure to nitrous oxide. Moreover, our patient had an inborn error of metabolism in an essential precursor in a metabolic pathway, rather than an acquired deficiency, and nitrous oxide was delivered on two occasions only a few days apart. Severe MTHFR deficiency is an autosomal recessive disorder characterized by progressive hypotonia, convulsions, and psychomotor retardation. The clinical presentation may be subtle, with the disorder manifested as developmental disability in the setting of moderate homocystinuria and hyperhomocysteinemia and low-to-normal levels of plasma methionine.29 Twenty-nine mutations in MTHFR are associated with severe deficiency, with a resulting activity level that is usually 0 to 30 percent of control activity.7,8,14,30,31,32,33 Most patients are heterozygous for multiple MTHFR substitutions; a small minority are homozygous for mutations at this locus. The 1755G ---------- A substitution identified in our patient occurs in a phylogenetically conserved region of the MTHFR protein (as assessed with BLASTP software, version 2.2.1). This region, which is thought to be essential for functional protein folding,34 is a " hot spot " for mutations leading to MTHFR deficiency (1711C ---------- T, 1727C ---------- T, 1762A ---------- T, and 1768G ---------- A).7,8 The heterozygous presence of the 1755G ---------- A substitution in the patient's father, brother, one uncle, and one aunt and its absence in 100 independent control chromosomes suggest that it is not a benign variant. Compound heterozygosity for the common MTHFR alleles 677C ---------- T and 1298A ---------- C, as seen in the patient, his mother, and his brother, causes elevations in the plasma homocysteine level4 that are associated with a 50 to 60 percent decrement in enzyme activity.35 In the absence of coding mutations elsewhere in the MTHFR gene or evidence of a mutant splice variant, our patient's deficient enzyme activity may be attributable to compound heterozygosity for the novel 1755G ---------- A mutation, with the prevalent 677C ---------- T polymorphism on the same (paternal) chromosome and the 1298A ---------- C mutation on the maternal chromosome. It has recently been shown that when mutations causing severe MTHFR deficiency are expressed in cis configuration with the common 677C ---------- T variant, the resultant phenotype is markedly aggravated.34 Every year, approximately 45 million persons in North America undergo anesthesia, and nitrous oxide constitutes a major component in about half these procedures.36 Because of the growing use of nitrous oxide,37,38,39,40,41 patients with known mutations associated with mild or severe abnormalities in folate-cycle enzymes are increasingly likely to receive nitrous oxide. On the strength of the current findings, we believe that patients with a diagnosis of severe MTHFR deficiency should not receive nitrous oxide as anesthesia. In the case of emergency procedures, patients whose clinical presentation fits that of severe MTHFR deficiency, even if the disorder has not been diagnosed, should also not receive nitrous oxide. In the case of elective procedures, patients whose clinical presentation fits that of severe MTHFR deficiency should be evaluated, and the diagnosis should be ruled out before anesthesia with nitrous oxide is contemplated. Supported by grants from the Doris Duke Foundation and the University of Wisconsin Department of Anesthesiology Research and Development Fund (to Dr. Hogan) and the Canadian Institutes of Health Research (to Dr. Rosenblatt). We are indebted to Singh Sekhon, Ph.D. (University of Wisconsin, Madison), for the fibroblast cultures and to H. , M.D. (Metabolite Laboratories, Denver), for the assays of total homocysteine. Source Information From the Departments of Anesthesiology (R.R.S., K.H.) and Medical Genetics (R.L.), University of Wisconsin Medical School, Madison; and the Departments of Human Genetics, Medicine, Pediatrics, and Biology, McGill University, Montreal (D.S.R.). Address reprint requests to Dr. Hogan at the Department of Anesthesiology, B6/319 Clinical Sciences Center, 600 Highland Ave., Madison, WI 53792, or at khogan@.... References 1. Chiang PK, Gordon RK, Tal J, et al. S-adenosylmethionine and methylation. FASEB J 1996;10:471-480.[Abstract] 2. Beckman DR, Hoganson G, Berlow S, Gilbert EF. Pathological findings in 5,10-methylene tetrahydrofolate reductase deficiency. Birth Defects Orig Artic Ser 1987;23:47-64.[Medline] 3. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-113.[iSI][Medline] 4. van der Put NM, Gabreels F, s EM, et al. A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 1998;62:1044-1051.[CrossRef][iSI][Medline] 5. Kanwar YS, Manaligod JR, Wong PW. Morphologic studies in a patient with homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency. Pediatr Res 1976;10:598-609.[Abstract] 6. Rosenblatt DS, Erbe RW. Methylenetetrahydrofolate reductase in cultured human cells. I. Growth and metabolic studies. Pediatr Res 1977;11:1137-1141.[iSI][Medline] 7. Sibani S, Christensen B, O'Ferrall E, et al. Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum Mutat 2000;15:280-287.[CrossRef][iSI][Medline] 8. Kluijtmans LA, Wendel U, s EM, van den Heuvel LP, Trijbels FJ, Blom HJ. Identification of four novel mutations in severe methylenetetrahydrofolate reductase deficiency. Eur J Hum Genet 1998;6:257-265.[CrossRef][iSI][Medline] 9. Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics 2001;1:189-201. 10. Harmon DL, Shields DC, Woodside JV, et al. Methionine synthase D919G polymorphism is a significant but modest determinant of circulating homocysteine concentrations. Genet Epidemiol 1999;17:298-309.[CrossRef][iSI][Medline] 11. A, Platt R, Wu Q, et al. A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab 1999;67:317-323.[CrossRef][iSI][Medline] 12. Tsai MY, Bignell M, Schwichtenberg K, Hanson NQ. High prevalence of a mutation in the cystathionine beta-synthase gene. Am J Hum Genet 1996;59:1262-1267.[iSI][Medline] 13. Gaughan DJ, Barbaux S, Kluijtmans LA, Whitehead AS. The human and mouse methylenetetrahydrofolate reductase (MTHFR) genes: genomic organization, mRNA structure and linkage to the CLCN6 gene. Gene 2000;257:279-289.[CrossRef][iSI][Medline] 14. Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet 1994;7:551-551. 15. Homberger A, Linnebank M, Winter C, et al. Genomic structure and transcript variants of the human methylenetetrahydrofolate reductase gene. Eur J Hum Genet 2000;8:725-729.[CrossRef][iSI][Medline] 16. Frasca V, Riazzi BS, s RG. In vitro inactivation of methionine synthase by nitrous oxide. J Biol Chem 1986;261:15823-15826.[Abstract/Full Text] 17. Christensen B, Rosenblatt DS, Chu RC, Ueland PM. Effect of methionine and nitrous oxide on homocysteine export and remethylation in fibroblasts from cystathionine synthase-deficient, cblG, and cblE patients. Pediatr Res 1994;35:3-9.[Abstract] 18. Fiskerstrand T, Ueland PM, Refsum H. Folate depletion induced by methotrexate affects methionine synthase activity and its susceptibility to inactivation by nitrous oxide. J Pharmacol Exp Ther 1997;282:1305-1311.[Abstract/Full Text] 19. Kondo H, Osborne ML, Kolhouse JF, et al. Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats. J Clin Invest 1981;67:1270-1283.[iSI][Medline] 20. Koblin DD, Waskell L, JE, Stokstad EL, Eger EI II. Nitrous oxide inactivates methionine synthetase in human liver. Anesth Analg 1982;61:75-78.[Abstract] 21. Royston BD, Nunn JF, Weinbren HK, Royston D, Cormack RS. Rate of inactivation of human and rodent hepatic methionine synthase by nitrous oxide. Anesthesiology 1988;68:213-216.[iSI][Medline] 22. Christensen B, Guttormsen AB, Schneede J, et al. Preoperative methionine loading enhances restoration of the cobalamin-dependent enzyme methionine synthase after nitrous oxide anesthesia. Anesthesiology 1994;80:1046-1056.[iSI][Medline] 23. Deacon R, Lumb M, J, et al. Inactivation of methionine synthase by nitrous oxide. Eur J Biochem 1980;104:419-423.[Abstract] 24. Molloy AM, Orsi B, Kennedy DG, Kennedy S, Weir DG, JM. The relationship between the activity of methionine synthase and the ratio of S-adenosylmethionine to S-adenosylhomocysteine in the brain and other tissues of the pig. Biochem Pharmacol 1992;44:1349-1355.[CrossRef][iSI][Medline] 25. Koblin DD, JE, Deady JE, Stokstad EL, Eger EI II. Inactivation of methionine synthetase by nitrous oxide in mice. Anesthesiology 1981;54:318-324.[iSI][Medline] 26. Riedel B, Fiskerstrand T, Refsum H, Ueland PM. Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase. Biochem J 1999;341:133-138.[CrossRef][iSI][Medline] 27. Felmet K, Robins B, Tilford D, Hayflick SJ. Acute neurologic decompensation in an infant with cobalamin deficiency exposed to nitrous oxide. J Pediatr 2000;137:427-428.[CrossRef][iSI][Medline] 28. McNeely JK, Buczulinski B, Rosner DR. Severe neurological impairment in an infant after nitrous oxide anesthesia. Anesthesiology 2000;93:1549-1550.[iSI][Medline] 29. Rosenblatt DS, Fenton WA. Inherited disorders of folate and cobalamin transport and metabolism. In: Scriber CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic & molecular bases of inherited disease. 8th ed. Vol. 3. New York: McGraw-Hill, 2001:3897-933. 30. Goyette P, Christensen B, Rosenblatt DS, Rozen R. Severe and mild mutations in cis for the methyelentetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR. Am J Hum Genet 1996;59:1268-1275.[iSI][Medline] 31. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 1995;56:1052-1059.[iSI][Medline] 32. Tonetti C, Amiel J, Munnich A, Zittoun J. Impact of new mutations in the methylenetetrahydrofolate reductase gene assessed on biochemical phenotypes: a familial study. J Inherit Metab Dis 2001;24:833-842.[CrossRef][iSI][Medline] 33. Homberger A, Linnebank M, Sewell A, Suormala T, Fowler B, Koch HG. Severe methylenetetrahydrofolate reductase deficiency: two novel genotypes with different clinical course. J Inherit Metab Dis 2001;24:Suppl 1:50-50. abstract. 34. Goyette P, Rozen R. The thermolabile variant 677C ---------- T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase. Hum Mutat 2000;16:132-138.[iSI][Medline] 35. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab 1998;64:169-172.[CrossRef][iSI][Medline] 36. Orkin FK, SJ. Scope of modern anesthetic practice. In: RD, ed. Anesthesia. 5th ed. Vol. 2. Philadelphia: Churchill Livingstone, 2000:2577-85. 37. Peretz B, Katz J, Zilburg I, Shemer J. Response to nitrous-oxide and oxygen among dental phobic patients. Int Dent J 1998;48:17-23.[iSI][Medline] 38. Keating HJ III, Kundrat M. Patient-controlled analgesia with nitrous oxide in cancer pain. J Pain Symptom Manage 1996;11:126-130.[CrossRef][iSI][Medline] 39. Luhmann JD, Kennedy RM, Porter FL, JP, Jaffe DM. A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. Ann Emerg Med 2001;37:20-27.[CrossRef][iSI][Medline] 40. Castera L, Negre I, Samii K, Buffet C. Patient-administered nitrous oxide/oxygen inhalation provides safe and effective analgesia for percutaneous liver biopsy: a randomized placebo-controlled trial. Am J Gastroenterol 2001;96:1553-1557.[CrossRef][iSI][Medline] 41. Krauss B. Continuous-flow nitrous oxide: searching for the ideal procedural anxiolytic for toddlers. Ann Emerg Med 2001;37:61-62.[CrossRef][iSI][Medline] ---------- ---------- ---------- ---------- PDF ---------- PDA Full Text ---------- Supplementary Material ---------- ---------- ---------- ---------- Perspective ---------- by Erbe, R. W. ---------- Letters ---------- ---------- ---------- ---------- Add to Personal Archive ---------- Add to Citation Manager ---------- Notify a Friend ---------- E-mail When Cited ---------- E-mail When Letters Appear ---------- ---------- ---------- ---------- Find Similar Articles ---------- PubMed Citation ---------- Related Letters: Nitrous Oxide and 5,10-Methylenetetrahydrofolate Reductase Burman J. F., Kaufman J. L., Hogan K., Erbe R. W. Extract | Full Text | PDF N Engl J Med 2003; 349:1479-1480, Oct 9, 2003. Correspondence This article has been cited by other articles: .. (2003). Lucina. Arch. Dis. Child. 88: 1142-1142 [Full Text] .. (2003). Fatal Combination: Nitrous Oxide Anesthesia and Methionine Pathway Defects. Journal Watch Neurology 2003: 5-5 [Full Text] .. Burman, J. F., Kaufman, J. L., Hogan, K., Erbe, R. W. (2003). Nitrous Oxide and 5,10-Methylenetetrahydrofolate Reductase. N Engl J Med 349: 1479-1480 [Full Text] HOME | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | HELP Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2004 Massachusetts Medical Society. All rights reserved. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 24, 2004 Report Share Posted September 24, 2004 I think many factors are at work here. Genetics , amount of exposure, liver metabolism.....who knows? People who recreationally use nitrous have presented to the ER complaining of numbness. In the article posted it seemed the factors were genetic and a long exposure time. Nitrous has been used for years in children and adults with no ill effects. I sure that sniffing this stuff for over 20 years has something to do with it. I now avoid nitrous with my adult patients as I feel this contributes to post op nausea and vomiting. The short amount of exposure that a child receives during an anesthetic should cause no problems. Sym Date: Fri, 24 Sep 2004 08:58:41 -0700 From: White Light <whitelight@...> Subject: Re: Re: anesthesia Pardon me for asking, but if your experiencing these symptoms from the possibility of nitrous and putting kids to sleep ..... what effect does that have on the children? That kind of scares me. Shauna [ ] Re: anesthesia i am a nurse anesthetist and I found this article on the internet. My child is on the spectrum and we are going to have MTHFR testing done. Currently I am taking folic acid for a high homocystine level( MTHFR defect). I have heard that they think this gene has something to do with folate metabolism which our kids need for metal metabolism. I have been practicing for over 20 years and when we put kids to sleep we use high flows of nitrous. Last year I started getting numbness in my face and arms. I had a cat scan and they found nothing wrong. But then I discovered I got the numbness after I did a room full of kids that day. Still trying to figure that one out but I am now trying not to do as many kids if possible. Pass this to your anesthesia friend....Sym Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 24, 2004 Report Share Posted September 24, 2004 Thanks for the information. I was just curious as I have had about 5 operations as a child where I was put under so I wondered if my exposure had contributed to my daughters condition. Shauna [ ] Re: anesthesia > > > i am a nurse anesthetist and I found this article on the internet. My > child is on the spectrum and we are going to have MTHFR testing done. > Currently I am taking folic acid for a high homocystine level( MTHFR > defect). I have heard that they think this gene has something to do > with folate metabolism which our kids need for metal metabolism. I > have been practicing for over 20 years and when we put kids to sleep we > use high flows of nitrous. Last year I started getting numbness in my > face and arms. I had a cat scan and they found nothing wrong. But > then I discovered I got the numbness after I did a room full of kids > that day. Still trying to figure that one out but I am now trying not > to do as many kids if possible. Pass this to your anesthesia > friend....Sym > > > > > ======================================================= > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted September 27, 2004 Report Share Posted September 27, 2004 Hi a, I just wanted to wish you luck on your operation and a speedy recovery. Susiea <twhwoman@...> wrote: I'm having both knees replaced this coming Wednesday, 9-29,and I discussed anesthesia with my doc. He said that whenyou have one done, they can give you an epidural, and lightgeneral anesthesia, but you may be somewhat aware of thegoings on in the O.R. When doing both knees, the choice is aspinal, or general, since they don't want you waking upduring the procedure, at all. I opted for general, since Iknow too many friends who have had complications with thespinal, like bad, recurring headaches for a couple of weeks,and worse. I will still have an epidural catheter with apump, for post surgical pain. A nurse friend had theepidural catch two months ago, and she raved about it. Shesaid she had almost no surgical pain after her kneereplacement. Of course I'm nervous, but mostly excited aboutbeing able to resume my life, travel, be active, all withoutthe horrible knee pain I've lived with for so many years.I went for a 3 1/2 hour trail ride today with four of myfriends, and my wonderful dogs, here in upstate NY. I liveon a small man, and the fall foliage is starting. Theweather was perfect, and we had a ball. This was my lastride of this season, and it was just perfect. When I askedmy doc how long it would take me to recover, he said about6-8 weeks. When I asked him if he would actually give me theokay to get on my horses in 8 weeks, he said YES, as long asI feel up to it. I sure hope he's right. Keep me in yourthoughts.................a Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 3, 2005 Report Share Posted January 3, 2005 Hi, I had a spinal and general anesthetic. The anaesthesiologist warned me that I did not want to wake up during surgery -- that the procedure could last a long time. When I did come to, I wasn't drowsy, and it didn't seem to affect my recovery because I left the hospital in two day. Carolethom42 <ethom42@...> wrote: I forgot to ask who has had a spinal with THR? I am scheduled for one with a sedative. I see the advantages over general, but I really don't want to know anything that is going on. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 4, 2005 Report Share Posted January 4, 2005 I had the same -- spinal + general anesthetic -- and it was fine. Had lunch a couple hours after I got back to my room. You definitely don't want to be aware during this surgery; it is noisy! S. -----Original Message-----From: Carol [mailto:carolann1312004@...] Sent: Monday, January 03, 2005 9:05 PMJoint Replacement Subject: Re: Anesthesia Hi, I had a spinal and general anesthetic. The anaesthesiologist warned me that I did not want to wake up during surgery -- that the procedure could last a long time. When I did come to, I wasn't drowsy, and it didn't seem to affect my recovery because I left the hospital in two day. Carolethom42 <ethom42@...> wrote: I forgot to ask who has had a spinal with THR? I am scheduled for one with a sedative. I see the advantages over general, but I really don't want to know anything that is going on. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted January 4, 2005 Report Share Posted January 4, 2005 I had an epidural with a sedative - I was out cold - I don't remember a thing. I have heard of a few people who " woke up " while in the OR - they said it was weird but not really scary. I don't think I'd like it. (48) RC2K Dr. Gross 3/24/04 > > I forgot to ask who has had a spinal with THR? I am scheduled for > one with a sedative. I see the advantages over general, but I > really don't want to know anything that is going on. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted June 16, 2005 Report Share Posted June 16, 2005 Lee,. I'm with you ... no interest in hearing all the sawing and pounding! Also, I was not about to let anyone stick a needle in my back. Just my quirk on that one, but I chose general anesthesia for both my THRs. Not ever having had the epidural, though, I can't compare recovery and post op pain. Anesthesia I apparently have my choice of anesthesias for this procedure... general or spinal. Doc recommended the spinal, but left it up to me. Said I'd get more pain relief (an hour or so) after surgery, and then, it would be an easier recovery than a general. What I DON'T want is to hear hammers and chisels and saws hacking away at my leg.... Any opinions???? lee ~ ~ ~ ~ ~ ~ Listen to the tide slowly turning, washes all our heartache awayWe’re part of the fire that is burningand from the ashes we can build another day(The Moody Blues “Story In Your Eyes”) Quote Link to comment Share on other sites More sharing options...
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