A 27 year old female underwent a total thyroidectomy for hyperthyroidism. The patient was being treated for intermittent bouts of tachycardia with a beta blocker and had been started on propylthiouracil. The patient underwent general anesthesia that included sevoflurane in oxygen, fentanyl for pain control, glycopyrrolate 0.2 mg, midazolam 2mg, vecuronium, propofol for induction, and two doses of zofran (one at the beginning of the case and one at the end of the case) of 4 mg each. The surgery was unremarkable and lasted aproximately 90 minutes. The patient was allowed to emerge and was extubated in the OR and transported to the PACU on oxygen. In the PACU, it was noticed that the patient was not responding to commands and thereafter was not responding to painful stimuli. Her respiratory rate and pupils did not indicate that she was narcotized, nevertheless, two small doses of naloxone were given (40 mcg each). This did not result in any change in her status. Romazicon was attempted, 0.1 mg times 2, 5 minutes apart without benefit. At this time a quick check of possible etiologies for delayed emergence was undertaken. The differential for an otherwise healthy female who fails to emerge from anesthesia in a timely fashion should consider the most likely causes first based on history.
The work up for delayed emergence began in our case with the most common reasons: too much narcotic, inhalational anesthetic or anxiolytic. After considering residual anesthetic effects in a patient who experiences delayed emergence, a rapid check of the other common causes is undertaken. These include acute intoxication from recreational agents (drugs, EToH), residual neuromuscular blockade, ventilatory failure resulting in somnolence from hypercarbia, and metabolic derangements such as hypo/hyperglycemia, hyponatremia. Other causes are hypothermia, hypoxic brain injury, hypoxemia, or neurological insult such as ischemia, or hemorrhagic stroke, or acute increase in ICP. In most cases, the above causes of delayed emergence are either iminently obvious, or can be quickly ruled out by history and context.
In our case an extensive effort was undertaken to rule out all of the above including EEG and CT. EEG was ordered by the consulting neurologist to rule out complex partial status epilepticus or absence status epilepticus, which are non convulsive constant seizure activity. Unfortunately, no obvious cause for our patients comatose state was apparent and it was decided to admit her to the ICU for further observation.
In 1988, a 5 year old boy presented for surgery. He received oral midazolam for anxiolysis, and a short volatile anesthetic. Postoperatively the boy experienced an unusual emergence, was given a small dose of physostigmine and improved dramatically. The diagnosis of central anticholinergic syndrome was offered in the published case report. Indeed, there are many case reports in the literature describing patients with unusual emergence characteristics that have been attributed to CAS. (5,6,7)
CAS presentation is variable with symptoms including: ataxia, dry mouth and throat, cessation of perspiration (leads to hyperthermia), mydriasis (results in photophobia), cycloplegia (leading to blurry vision), tachycardia, urinary retention, increased IOP, shaking, confusion, agitation, hallucinations, respiratory depression, myoclonic jerking, and coma. The central anticholingergic syndrome (CAS) typically results from drugs that act to inihibit or compete with acetylcholine in the CNS where it plays a critical role in arousal states and REM sleep. Physostigmine is a tertiary amine that penetrates the blood brain barrier and inhibits the breakdown of acetylcholinesterase, leading to increased acetylcholine in the synaptic cleft. In fact, while CAS is a difficult diagnosis and typically requires excluding other causes first, a clinical response to physostigmine is indicative that CAS is the cause.
While in some cases it is clear that a patient may have developed CAS a reaction to anticholinergic drugs such as atropine or scopolamine, it is often less commonly realized that our typical intravenous and volatile anesthetics can induce CAS as well.
Indeed, physostigmine has been utilized as a reversal agent for general anesthetics and there are case reports of physostigmine reversing benzodiazepines, opioid narcotics, volatile anesthetics, ketamine, and propofol. However, prospective double blind studies have failed to find a benefit when given to reverse benzodiazepines or opioid narcotics. On the other hand, in a series of nine patients sedated with propofol and monitored with a BIS monitor, phyosostigmine was effective in reversing sedation in 7 of the patients. (3) In this study, it was shown that an iv dose (~0.4mg) of scopolamine prior to physostigmine prevented reversal of propofol anesthesia. This indicates that muscarinic acetylcholine receptors are at least in part responsible for the sedative effects of propfol. Whether propofol causes sedation and a sleep like state by interfering with the central cholinergic neurotransmission directly or indirectly is unknown. It is thought that propofol binds to the GABAa receptor to induce anesthesia. Furthermore, it has been shown that GABAergic stimulation in the medial pontine reticular formation inhibits acetylcholine release resulting in arousal and inhibition of the REM sleep like state. Other brain regions also play a role GABAergic modulation of acetlycholine release to effect arousal and sedation in animals. Further evidence for propofol's action on the central cholinergic system is provided by another study showing that the dose of propfol required to induce anesthesia is slightly higher in patients given physostigmine. (8) It is also proposed that volatile anesthetics bind to GABAa receptors. Central cholinergic transmission is also effected by volatile anesthetics. In animal models, increased cholinergic transmission antagonizes halothane, isoflurance and sevoflurane anesthesia respectively. (3,11) In humans, Hill and collegues (9)reported that physostigmine was able to decrease the time to return to consciouness after halothane anesthesia indicating the cholinergic transmission is important in arousal after anesthesia. Physostigmine was also shown to partially reverse sevoflurane anesthesia, although physostigmine was not as effective as it was in reversing propofol. (10) However, Paraskeva A and collegues was unable to show BIS reversal or improved recovery using physostigmine in patients receiving sevoflurane. (12)
The central anticholinergic syndrome may be an underrecognized syndrome in patients who receive anesthesia. One report(4) found an incidence of 1.8% in patients who underwent general anesthesia for a myriad of conditions. In the same report, they found that women who underwent a hysterectomy had a higher incidence of CAS (10%). Because of the variable presentation of CAS and the relative frequency of its appearance in controlled trials, it is likely that thousands of patients a year suffer medical work ups or delays in discharge as clinicians attempt to deal with delayed or unusual emergence phenomena.
The neurobiology of sleep and arousal states is complex. However, studies are beginning to tease out the brain areas that play a role in maintaining anesthesia and causing arousal. It has become increasingly evident that altered central cholinergic transmission mediates the anesthetic state. Recent work in rats demonstrated that the nACHr may play the role of an "on" switch in anesthesia (2) (i.e. stimulation of this receptor can awake the patient). It has been shown that the sleep-wake cycle as well as the maintenance of the awake state is dependent on cholinergic neurotransmission from the medial pontine reticular formation as well as other important centers, such as the basal forebrain, thalamus, medial preoptic nucleus, and locus coeruleus.
We know that acetylcholine is critical for both arousal and cognition. For example, Carbachol (muscarinic Ach agonist) injected directly into the medial pontine reticular formation can cause a REM like sleep (EEG appearance is similar to the awake state) but also can reverse halothane anesthesia which shares a similar EEG pattern to Non REM sleep. Additionally, it is known that cortical acetylcholine release is increased during both REM sleep (EEG appearance same as awake state) and in the awake state. Conversely, Acetylcholine release is decreased during both anesthesia and during non REM sleep. This concept is important to understand as we next look at the various anesthetics and how they are known to effect either directly or indirectly acetylcholine neurotransmission.
Both opioids and ketamine have been shown in animal models to affect acetylcholine neurotransmission; i.e. they can result in decreased acetylcholine release resulting in decreased arousal. Likewise, the volatile anesthetics can result in decreased acetylcholine release when placed directly in the pontine reticular formation (important in modulating arousal and sleep). These studies are inline with the clinical work sited above wherein physostigmine (increases acetylcholine) can reverse at least partially anesthesia by propofol and inhalational agents. Acetylcholine is not the only neurotransmitter that plays a role in arousal and sleep states. When ATP is cleaved for metabolic activity in the brain, adenosine is a byproduct. This neurotransmitter has been shown to increase the drive for sleep as its levels increase in the brain. Furthermore, adenosine receptor type 1 agonists when applied to the arousal/sleep center of the brain, the pontine reticular formation will delay recovery from halothane anesthesia. A1 receptors are also thought to play a role in isoflurane anesthesia and this all combined helps explain why caffeine is utilized to avoid or delay sleep since it works as an adenosine antagonist.
GABA plays a complicated role in human sleep/wake cycles. GABAergic neurotransmission in several different key nuclei (basal forebrain, preoptic nucleus of the hypothalamus, locus coeruleus and dorsal raphe nucleus) acts to modulate arousal and sleep. It is believed that it can do so by inhibiting acetylcholine release from key neurons. Many anesthetics are believed to act directly on the GABAa receptor, and in this way alone, are capable of modulating acetylcholine levels in the key sleep/arousal centers as well as in the cerebral cortex generally where muscarinic receptors are known to modulate arousal.
As mentioned above, the raphe nucleus (both midline and dorsal) and locus coeruleus play a role in sleep/wake cycles in humans. In particular, these nuclei discharge maximally during the awake state, and progressively decrease their discharge during non REM and REM sleep respectively. In addition, serotonin is known to aid in arousal (via the midline raphe nucleus), histamine aids in arousal via the posterior hypothalamus, Norepinephrine aids in arousal from the locus coeruleus, and dopamine has varying affects on the sleep wake cycle that are complicated and not fully eludcidated. Recent research has shown a role for hypocretin I and II (also known as orexin A and B) in arousal. Located in the hypothalamus with connections to important areas controlling arousal, these brain peptides are believed to play a role in narcolepsy, or rapid onset of REM sleep. Therefore, emergence from anesthesia involves a host of different neurotransmitters interacting in a complex manner in a variety of different brain nuclei. This complex interaction depends upon a careful balance of inhibition and stimulation and consequently, patients who do not emerge in an expected manner may have an increase or decrease of one or more of these systems. Fortunately, it appears that in most cases, increasing cholinergic neurtransmission (via physostigmine) can attenuate or even reverse delayed emergence when caused by unbalanced neurotransmission.
Physostigmine is often given in a dose of 30 mcg/kg and often with glycopyrrolate to offset peripheral actions of acetylcholine (bradycardia, ileus, urinary retention). Physostigmine is often associated with nausea and in some cases has been associated with ventricular arrythmias, atrial fibrillation and hypertension. Therefore, patients who receive physostigmine should have heart monitoring. The clinical duration is 35 to 45 minutes. In many cases, patients become reobtunded. Multiple dosages are often required.
Finally, delayed or unusual emergence is not uncommon and in many cases may represent continued blockade of cholinergic neurotransmission which is known to be affected by virtually all of our anesthetic medications. Diagnosis by trial of physostigmine is reasonable once other causes of delayed emergence are ruled out. Continued monitoring of these patients is required and in some cases admission to the ICU may be indicated.
1. Hagemann HD, Prass D, Hausdorfer J. A case of central anticholingergic syndrome in pediatric anesthesia. Anaesthesist 1988;37:193-5.
2. Alkire MT, McReynolds JR, Hahn EL et al. Thalamic microinjection of Nicotine Revereses Sevoflurane induced Loss of Righting Reflex in the Rat. Anesth 2007;107:264-72.
3. Meuret P, Backman SB, Bonhomme V et al. Physostigmine Reverses Propofol-induced Unconsciousness and Attenuation of the Auditory Steady State Response and Bispectral Index in Human Volunteers. Anesthesiology 2000;93:708-17.
4. Link J, Papadopoulos G, Dopjans D, et al. Distinct central anticholingergic syndrome following general anesthesia. Eur J Anesthesiol 1997; 14:15-23.
5. Kulka PJ, Toker H, Heim J, Joist A, and Jakschik J. Suspected Central Anticholinergic Syndrome in a 6 Week Old Infant. A&A 2004; 99:1376.
6. Kati I, Demirel CB, Anlar O, et al. An unusual complication of total Intravenous anesthesia: Mutism. A&A 2003; 96:168-70.
7. Kaiser-Stadler M, Altmayer P. CAS after propofol anesthesia. Anesthesiol Intensivmed. Notfallmed Schmerzther 1995;30:116-7.
8. Can J Anesth 1977;44:1148
9. Hill GE, Stanley TH, Sentker CR. Physostigmine reversal of postoperative somnolence. Can Anesth Soc J 1977;24:707-11.
10. Plourde G, Chartrand D, Fiset P, Font S. Backman SB. Antagonism of sevoflurane anesthesia by physostigmine: effects on the auditory steady-state response and BIS. B J Anesthesia 2003; 91:583.
11. Hudetz AG, Wood JD, Kampine JP. Cholinergic reversal of isoflurane anesthesia in rats as measured by cross-approximate entropy of the EEG. Anesth 2003;99:1125.
12. Paraskeva A, Papilas K, Fassoulaki A, Melemeni A, Papadopoulos G. Physostigmine does not antagonize sevoflurane anesthesia assessed by BIS or enhance recovery. A&A 2002:94:569-72.
March 16, 2010
March 9, 2010
Obstetrical Hemorrhage-A near Miss
On a previously quiet Monday afternoon I received a call from the OB floor. "we are going for a stat c/s" was the report given by the nurse. I headed immediately towards the OB OR. I encountered the patient at the elevators leading to the 6th floor. I breifly got a history from the nurses accompanying the patient. She was 36 years old at 36 weeks gestation. She was experiencing brisk vaginal bleeding associated with severe abdominal cramps and pain. The ambulance decided to divert to our hospital because of the urgency of the situation. She was wheeled straight to the OR and hooked up to monitors. I found out that she had a history of hypertension taking Labetalol, w/ NKDA. She was also known to have a placenta previa w/ possible accreta. She was scheduled by her regular obstetrician to undergo a planned cesarian section and hysterectomy a week or so.
Preinduction VS: BP 120/60 HR 110 RR: rapid sats: 98%. Pt expressing pain and is anxious.
Induction is with ketamine 100mg, fentanyl 50 mcg, sux 90 mg all in rapid sequence with cricoid pressure. After incision, the infant was delivered in 1 minute, and is not in distress.
The patient tolerates induction, has 2 IV lines (20G L and 18G R). Within 5 minutes of induction the plethysmographer tracing goes flat and no blood pressure is able to be recorded. 3 mg of phenylephrine is given IV and the blood pressure returns to 90s/40s. The patient is not typed or crossed so type 0 negative blood is procured on an emergent basis and 2 units of O- PRBCs are given over 20 minutes. A R IJ central line and L rad arterial line are placed with some difficulty. Hemostasis is obtained within 10 minutes of incision. The patient experiences only two more episodes of severe hypotension (30's/10's) and (50's/20's) both treated with epinephrine 0.5 mg bolus. A hysterectomy is performed, ancef 1 gm is given IV, versed is given 2 mg to prevent recall along w/ scopolamine 0.4 mg IV. The patient is intermittent run on 50% nitrous oxide and Desflurane depending on blood pressures. The patient makes 200 mL's of urine for the case, receives 3.5 L crystalloid, 2 u PRBCs (O-), 500 mLs hespan, and EBL is 1500 mL. During the case it is discovered that from faxed medical records she is A- and the specimen states that she has antibodies. The patient remains intubated and is transferred to the ICU. Because she is starting to develop hypotension again, the decision is made to transfuse her units of blood, this time A- matched blood. A Hg drawn after her first two units is 7.9 g/dl. The patient did continue to have brisk bleeding from the vagina immediately after surgery, but this was controlled and no oozing occurred from her central line site or arteral line site. After surgery her PTT came back at >200s (significantly prolonged), however, her fibrinogen level was only mildly low with a normal PT and INR. Upon arrival to the ICU she was 34 C.
This represents a case of severe maternal hemorrhage associated with placental abruption and placenta increta (discovered at operation). Placental abruption is not uncommon occurring in 1/100 to 1/150 deliveries, but is not commonly as severe as in this particular patient. It carries of perinatal mortality of 20%, so rapid delivery is often mandated for fetal and maternal salvage. This patient did have a few risk factors for abruption including advanced maternal age (36 y/o) and history of hypertension. Other risk factors, African american race, multiparity, cigarette smoking and cocaine abuse were either negative or unknown. Patients who experience abruption of the placenta are at high risk for DIC as demonstrated by Gilabert and colleagues in 1985. They explained that large venous sinuses beneath the abrupted placenta could allow thrombopastic material to enter the maternal circulation. Fortunately, in this patient no signs or evidence of DIC presented itself.
Treating hemorrhagic shock typically involves ensuring the maintenance of DO2. Since DO2=CO X (Hb x 1.34 x SaO2) + (PaO2 x 0.0031), maintaining an adequate cardiac output and Hb level are the principal factors. Secondarily, O2 extraction at the tissue level can compensate for decreased DO2. PaO2 in this regard is insignificant and the saturation is usually not so low as to be rendered clinically important in this regard. Initially, colloids and crystalloids should be utilized to maintain cardiac output, which in healthy individuals will easily compensate for a lowered Hb and in some cases DO2 may be elevated after hemorrhage compensated by crystalloid infusion due to improved rheologic effects.
In our case it was decided to transfuse unmatched type O negative blood. According to the ASA committee on transfusion medicine (4th edition), it is recommended to give uncrossmatched type 0 negative blood only when the patient is experiencing signs of organ dysfunction related to decreased O2 delivery. In males and post menopausal females, it is recommneded that type O positive be used. Only 20% of the population is considered Rh -, and therefore, type O Rh-negative blood is less common and should be utilized only when necessary. The concern is that giving a female who is still may yet have children in the future, you may cause her to develop anti-D antibodies (or antibodies against the D antigen in the Rh system). This is referred to as sensitization. In other words, giving type O-positive blood is unlikely to cause any reaction at all to any one unless they are Rh-negative and already sensitized (unlikely unless they have had previous transfusions or pregnancies). In historical studies, patients will develop anti-D antibodies about 80% of the time if they are Rh-D negative and are exposed to Rh positive blood. However, recent studies in trauma victims who require massive ressuscitation with fluid and blood products have found that sensitization occurs in only 30% of these individuals. It is hypothesized that the intense stress response brought on by the trauma or illness suppresses the normal immune response and reduces the likelihood of sensitization. In our case, our patient was required to have a cesarian section followed by hysterectomy and furthermore had received Rhogam. Therefore, O Rh positive blood would probably have been a better choice in retrospect so as to conserve the more rare type O Rh-negative blood. Some may question this approach given that our patient had received Rhogam which acts by destroying fetal RBCs that cross into the maternal circulation. In this case, one might suppose that the Rh immunoglobulin still circulating in the mother, might destroy RBCs transfused if they were type O positive. The standard dose is 300 mcg, and this only destroys about 15 mL of RBCs.
One other caveat in our patient is that she was positive for antibodies, although nothing more was specified. Our pt was type A Rh-negative. This indicates that she most likely received Rhogam (Antibodies) to prevent sensitization of the mother to fetal Rh-positive antigens, thus causing risk in future pregnancies for hemolytic disease of the newborn, a disease in which the fetus' RBCs are attacked as foreign by antibodies that manage to cross the placenta from the mother. Receiving Anit-D antibodies (Rhogam) will cause a subsequent type and screen to show antibodies, but they are unlikely to cause problems. Regardless of whether she had actual antibodies on the type and screen or not, given the patient's dire clinical situation, an emergency transfusion was indicated.
In our patient a sample was immediately sent to the blood bank to do a type and screen. However, in the mean time, 2 units of type O negative blood was given. The type and screen took 15 minutes and a electronic match was performed so that we had type A negative blood in only 30 minutes. A question was raised as to whether the patient could receive her type specific blood now after having received two units of type O negative blood. According to Yao and Artusio textbook, referring to published ASA guidelines, it is recommended to continue using type O negative blood if whole blood is given after only two units. However, whole blood is rarely used today, and the amount of serum in packed cells is very small and quickly diluted into the volume of blood in the patient. Therefore, the recommendation is to switch back to type specific blood even after several units of type O negative packed RBCs. At our institution, the blood bank does not specify a cut off for the number of type O negative blood given before we are unable to switch back to type specific blood.
When a type and screen is done, the screen portion refers to the mixing of the patient's serum with a commercially available donor RBC reagents. RBC surfaces contain up to 300 different antigens. In patients who have not been exposed to blood (transfusion or pregnancy), it is very unlikely that there will be unanticipated antibodies. In these cases, autoantibodies are the most likely culprit of a postive antibody screen. However, it is important to send the blood in a purple top tube (which contains EDTA to prevent a false positive). Certain medications may also result in a false positive: Ibuprofen, penicillins, cephalosporins, tetracyclines, antihistamines, sulfonamides, levodopa, methyldopa are a few of the most notorious ones. Furthermore, an autocontrol may be run and result in a positive. This test reacts the patients serum against their own RBCs and if positive should be followed by a direct antiglobulin test. The Type and Screen takes about 10 minutes. Not all antibodies are clinically relevant, however, when the screen comes back positive for antibodies, i.e., the patient's serum contains antibodies that might cause a hemolytic reaction to a transfusion, the antibody type is not known until further investigation. Clinically significant antibodies are: Anti-A,B, D, C, E, c, e, Fya, Fyb, Kell, Jka, Jkb, S, and s.
In summary, in an emergency use type O Rh positive blood unless you are transfusing a female is might become pregnant in the future; in this case use the more rare blood type O Rh-negative. In an emergency, always send a type and screen even if you are planning on using type O blood and switch to type specific blood as soon as possible. If the screen comes back positive for antibodies, a brief discussion with the lab is in order to find out if this occured at room temperature or at 37C (temp the screen should be done at). In some cases a false positive will occurr (due to medications or treatment received as in our patient Rhogam). Armed with this information, a benefit to risk analysis should ensure quickly to determine whether or not a transfusion is merited in the face of a known positive screen for antibodies.
Preinduction VS: BP 120/60 HR 110 RR: rapid sats: 98%. Pt expressing pain and is anxious.
Induction is with ketamine 100mg, fentanyl 50 mcg, sux 90 mg all in rapid sequence with cricoid pressure. After incision, the infant was delivered in 1 minute, and is not in distress.
The patient tolerates induction, has 2 IV lines (20G L and 18G R). Within 5 minutes of induction the plethysmographer tracing goes flat and no blood pressure is able to be recorded. 3 mg of phenylephrine is given IV and the blood pressure returns to 90s/40s. The patient is not typed or crossed so type 0 negative blood is procured on an emergent basis and 2 units of O- PRBCs are given over 20 minutes. A R IJ central line and L rad arterial line are placed with some difficulty. Hemostasis is obtained within 10 minutes of incision. The patient experiences only two more episodes of severe hypotension (30's/10's) and (50's/20's) both treated with epinephrine 0.5 mg bolus. A hysterectomy is performed, ancef 1 gm is given IV, versed is given 2 mg to prevent recall along w/ scopolamine 0.4 mg IV. The patient is intermittent run on 50% nitrous oxide and Desflurane depending on blood pressures. The patient makes 200 mL's of urine for the case, receives 3.5 L crystalloid, 2 u PRBCs (O-), 500 mLs hespan, and EBL is 1500 mL. During the case it is discovered that from faxed medical records she is A- and the specimen states that she has antibodies. The patient remains intubated and is transferred to the ICU. Because she is starting to develop hypotension again, the decision is made to transfuse her units of blood, this time A- matched blood. A Hg drawn after her first two units is 7.9 g/dl. The patient did continue to have brisk bleeding from the vagina immediately after surgery, but this was controlled and no oozing occurred from her central line site or arteral line site. After surgery her PTT came back at >200s (significantly prolonged), however, her fibrinogen level was only mildly low with a normal PT and INR. Upon arrival to the ICU she was 34 C.
This represents a case of severe maternal hemorrhage associated with placental abruption and placenta increta (discovered at operation). Placental abruption is not uncommon occurring in 1/100 to 1/150 deliveries, but is not commonly as severe as in this particular patient. It carries of perinatal mortality of 20%, so rapid delivery is often mandated for fetal and maternal salvage. This patient did have a few risk factors for abruption including advanced maternal age (36 y/o) and history of hypertension. Other risk factors, African american race, multiparity, cigarette smoking and cocaine abuse were either negative or unknown. Patients who experience abruption of the placenta are at high risk for DIC as demonstrated by Gilabert and colleagues in 1985. They explained that large venous sinuses beneath the abrupted placenta could allow thrombopastic material to enter the maternal circulation. Fortunately, in this patient no signs or evidence of DIC presented itself.
Treating hemorrhagic shock typically involves ensuring the maintenance of DO2. Since DO2=CO X (Hb x 1.34 x SaO2) + (PaO2 x 0.0031), maintaining an adequate cardiac output and Hb level are the principal factors. Secondarily, O2 extraction at the tissue level can compensate for decreased DO2. PaO2 in this regard is insignificant and the saturation is usually not so low as to be rendered clinically important in this regard. Initially, colloids and crystalloids should be utilized to maintain cardiac output, which in healthy individuals will easily compensate for a lowered Hb and in some cases DO2 may be elevated after hemorrhage compensated by crystalloid infusion due to improved rheologic effects.
In our case it was decided to transfuse unmatched type O negative blood. According to the ASA committee on transfusion medicine (4th edition), it is recommended to give uncrossmatched type 0 negative blood only when the patient is experiencing signs of organ dysfunction related to decreased O2 delivery. In males and post menopausal females, it is recommneded that type O positive be used. Only 20% of the population is considered Rh -, and therefore, type O Rh-negative blood is less common and should be utilized only when necessary. The concern is that giving a female who is still may yet have children in the future, you may cause her to develop anti-D antibodies (or antibodies against the D antigen in the Rh system). This is referred to as sensitization. In other words, giving type O-positive blood is unlikely to cause any reaction at all to any one unless they are Rh-negative and already sensitized (unlikely unless they have had previous transfusions or pregnancies). In historical studies, patients will develop anti-D antibodies about 80% of the time if they are Rh-D negative and are exposed to Rh positive blood. However, recent studies in trauma victims who require massive ressuscitation with fluid and blood products have found that sensitization occurs in only 30% of these individuals. It is hypothesized that the intense stress response brought on by the trauma or illness suppresses the normal immune response and reduces the likelihood of sensitization. In our case, our patient was required to have a cesarian section followed by hysterectomy and furthermore had received Rhogam. Therefore, O Rh positive blood would probably have been a better choice in retrospect so as to conserve the more rare type O Rh-negative blood. Some may question this approach given that our patient had received Rhogam which acts by destroying fetal RBCs that cross into the maternal circulation. In this case, one might suppose that the Rh immunoglobulin still circulating in the mother, might destroy RBCs transfused if they were type O positive. The standard dose is 300 mcg, and this only destroys about 15 mL of RBCs.
One other caveat in our patient is that she was positive for antibodies, although nothing more was specified. Our pt was type A Rh-negative. This indicates that she most likely received Rhogam (Antibodies) to prevent sensitization of the mother to fetal Rh-positive antigens, thus causing risk in future pregnancies for hemolytic disease of the newborn, a disease in which the fetus' RBCs are attacked as foreign by antibodies that manage to cross the placenta from the mother. Receiving Anit-D antibodies (Rhogam) will cause a subsequent type and screen to show antibodies, but they are unlikely to cause problems. Regardless of whether she had actual antibodies on the type and screen or not, given the patient's dire clinical situation, an emergency transfusion was indicated.
In our patient a sample was immediately sent to the blood bank to do a type and screen. However, in the mean time, 2 units of type O negative blood was given. The type and screen took 15 minutes and a electronic match was performed so that we had type A negative blood in only 30 minutes. A question was raised as to whether the patient could receive her type specific blood now after having received two units of type O negative blood. According to Yao and Artusio textbook, referring to published ASA guidelines, it is recommended to continue using type O negative blood if whole blood is given after only two units. However, whole blood is rarely used today, and the amount of serum in packed cells is very small and quickly diluted into the volume of blood in the patient. Therefore, the recommendation is to switch back to type specific blood even after several units of type O negative packed RBCs. At our institution, the blood bank does not specify a cut off for the number of type O negative blood given before we are unable to switch back to type specific blood.
When a type and screen is done, the screen portion refers to the mixing of the patient's serum with a commercially available donor RBC reagents. RBC surfaces contain up to 300 different antigens. In patients who have not been exposed to blood (transfusion or pregnancy), it is very unlikely that there will be unanticipated antibodies. In these cases, autoantibodies are the most likely culprit of a postive antibody screen. However, it is important to send the blood in a purple top tube (which contains EDTA to prevent a false positive). Certain medications may also result in a false positive: Ibuprofen, penicillins, cephalosporins, tetracyclines, antihistamines, sulfonamides, levodopa, methyldopa are a few of the most notorious ones. Furthermore, an autocontrol may be run and result in a positive. This test reacts the patients serum against their own RBCs and if positive should be followed by a direct antiglobulin test. The Type and Screen takes about 10 minutes. Not all antibodies are clinically relevant, however, when the screen comes back positive for antibodies, i.e., the patient's serum contains antibodies that might cause a hemolytic reaction to a transfusion, the antibody type is not known until further investigation. Clinically significant antibodies are: Anti-A,B, D, C, E, c, e, Fya, Fyb, Kell, Jka, Jkb, S, and s.
In summary, in an emergency use type O Rh positive blood unless you are transfusing a female is might become pregnant in the future; in this case use the more rare blood type O Rh-negative. In an emergency, always send a type and screen even if you are planning on using type O blood and switch to type specific blood as soon as possible. If the screen comes back positive for antibodies, a brief discussion with the lab is in order to find out if this occured at room temperature or at 37C (temp the screen should be done at). In some cases a false positive will occurr (due to medications or treatment received as in our patient Rhogam). Armed with this information, a benefit to risk analysis should ensure quickly to determine whether or not a transfusion is merited in the face of a known positive screen for antibodies.
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