Labetalol - FDA prescribing information, side effects and uses

So last night was interesting. Got a patient whose BP was in the 220's systolic on arrival to the ED, coupled with a syncopal event. The patient (we'll call them Scott) was given clonidine, labatalol, and diltiazem there and sent to me. Pressures on arrival to the floor were 160's. Scott was orthostatic positive with no reflex tachycardia d/t rate suppression by medication. He also had been recently started in metoprolol. Sinus bradycardia with a first degree AV block on the monitor.
The first night: uneventful. The patient stayed in the 160's, which the MD was okay with because he had been chronically high.
The second night: I get on shift. BP is 200/90, manually, in both arms. Rate in the 40's. No symptoms. I give the scheduled clonidine. Reassessment in 1 hour yields a BP of 210/80. I give the PRN diltiazem. Reassessment in 1 hour: 221/80! At this point, I give PRN labetalol, 10 mg, and also give all the night BP meds an hour early. A 15 minute check yields a BP of 190/80: Progress! But during this assessment, I note something I had never heard in this patient before: an auscultatory gap.
I call the MD, a resident, to update him. Weirdly enough, the patient had gone from 48 to 58 BPM after getting the metoprolol, one of the evening PO meds. The other was clonidine. The MD comes up to see the patient and confirms the gap. The pressure is back up in the 200's systolic, so I give another 10 of labetalol. No change this time.
I leave the patient with the night shift at a pressure of 221/80 with orders to give the patient hydralazine...
Patient history: End Stage Renal Disease d/t renal cell carcinoma. No cardiac history. No liver history. Mildly diabetic with diet control.
What are your thoughts?

Just finished a week of night call and I got called a lot to patients whose blood pressures were over 180/90 to assess them.
During my day team job my consultant would always tell us that unless the patients are severely symptomatic or there are signs of organ failure we do not need to treat acute hypertensive episodes with stat doses of nifedipine/labetalol. I went along with this and didn't give any meds to the asymptomatic pts and explained to the nurses to just keep an eye on it but they keep bleeping me every single time they do ops and it's high.
Would it be reasonable to give 1 stat dose of 10 mg nifedipine or 100 mg labetalol PO in these situations just to keep the bleep quiet?

I am extremely curious to know what happened to one of my patients, but I also do not want to give out too much information so as to reveal the patient's identity, so some negligible information will be inaccurate as to conceal the patient's identity in the event one of you may be familiar.
Female patient in her 50s enters the hospital 3 days ago with an exceedingly SMALL and insignificant intracranial hemorrhage that is managed by the neurosurgical and critical care medicine teams non-operatively. Patient's ONLY PMH is HTN, CAD with stents, and DM II. Patient, who is A/Ox4 and neuro intact recieves transfer orders to the floor one night. Upon readying patient for transfer, her SBP skyrockets above ordered parameters. It is early enough that scheduled PO meds are able to be given, as well as all PRNs. Labetalol IV is given with PO meds. No change. IV hydralazine is given--no change. Hospitalist (critical care team has signed off at this point) states to wait one hour from last PRN given before Cardene can be added, despite severe systolic hypertension (SBP >210). During this episode of HTN, patient's cardiac monitor soft alarms with a-fib, but P waves are visible. Appears to be new onset sinus pauses. An EKG reading is obtained by me and it states possible SA, AV block or sinus pause. Coincidentally, about this time, patient begins complaining of severe difficulty hearing. She states it sounds like someone is playing piano keys very loudly in her ears and I am having to shout very loudly directly next to the patient's head in order for her to hear me; patient has no PMH of hearing impairment and states this is entirely new. Neurosurgical team agrees to order STAT non-con head CT to rule out potential for temporal bleed extension. CT comes back 100% stable--nothing new and the initial bleed has almost entirely resolved.
Upon returning from CT, patient begins to explain that her hearing is returning and she is feeling better. Some time passes and suddenly, the patient's monitor shows she has removed her cardiac leads. I enter the room to find my once continent patient having had an episode of urinary incontinence. She is no longer verbal, not following commands, she has a disconjugate gaze (right eye out), and she has bilateral lateral nystagmus. Neurology is called and consulted and 2 mg IV Ativan is given STAT at the bedside. Patient worsens from here, soon becoming completely unresponsive to all external stimuli, develops sonorous respirations, pupils become very sluggish (once brisk), and a LUE tremor and rhythmic chewing motions are noted by neurology. Patient is intubated for airway protection and STAT EEG is ordered for suspected epileptiform activity. Once intubated, a STAT CT Angiogram of the head and neck are ordered to also rule out potential for a large vessel cerebral occlusion. Scans are completed in a timely fashion and all are stable and completely negative for any additional intracranial processes--absolutely nothing is wrong with the patient's brain it would seem.
Fast forward a few more hours, and after this patient has been skating by on 30 of prop and 5-12.5 of Cardene for a few hours, patient's SBP begins to plummet suddenly for seemingly no reason. Almost immediately, patient's HR falls to low-to-mid 40s and becomes arrhythmic, but still, all P waves, QRS complexes, and T waves are visible on the cardiac monitor. Cardene is immediately discontinued from 7.5, and prop is decreased to 10. Patient's pupils are fully blown and nonreactive now; she has no corneal reflexes, no cough, no gag, and completely flaccid in all extremities, and not breathing over the vent. Prop is d/c'd, 1 mg of IV atropine is given, 1 mg IV Neo-Synephrine is given, and patient is started on Levo drip at 20. Another 1 mg IV atropine is given--no increase in HR from low 40s. Dopamine is added at 10. Finally, an increase in BP and HR is appreciated, so we begin titrating down safely. I left my shift with the patient somewhat hemodynamically stable on 7 of Levo and off of dopamine. The last thing, and ONLY clue was a troponin of almost 3,000, but that was right before I left. ANY IDEAS???! Her GCS was still 3 when I left that morning and there was no improvement at all. She was supposed to be discharged home today without even PT/OT consulted. I am SO curious and also feel so guilty like I could have done something differently or noticed something else, or even thought of another possibility. If you have ever seen anything that presents as a seizure and stroke but with elevated cardiac enzymes, please enlighten me!!
[EDIT]: Wow, I did not realize this would perplex so many other people too. I will definitely, at this point, make a follow up post if I hear the answer! These are all great suggestions and I am goinf back to work in an hour so we will see if there is anything new!

I'm 32 year old white female. 5'1", 200 lbs. Current medications include Metformin 4 pills, 2x a day Labetalol, 1 pill, 1x a day Zoloft 100 mg, 1x a day Synthoid .37mg 1x a day Tri lol sprintec birth control 1x a day
So almost 2 weeks ago, my OBGYN upped the zoloft and started the birth control. That's about the time I started feeling really tired. I also had a positive coronavirus exposure during Thanksgiving. I'm literally sleeping whenever I can. I also have a 10 month old, which is why I'm so desperate to find a reason.
In January, I had an emergency c-section, due to preeclampsia and HELLP syndrome. That's why I'm on labetalol. Metformin is for PCOS. Zoloft is for depression. Synthoid is for hypothyroidism, after radioactive iodine for Graves Disease in 2017.

Age 38
Sex F
Height 5'10''
Weight 170
Race White
Duration of complaint
35-37 weeks gestational hypertension, postpartum preeclampsia began 6 days after birth, resolved with labetalol and 6 more weeks time. Now 20 months postpartum
Location US
Any existing relevant medical issues postpartum depression
Current medications 15 mg lexapro

Abstract
Objectives: Evaluating effect of oral labetalol pre-medication followed by low-dose intraoperative (IO) labetalol infusion on IO heart rate (HR) and mean arterial pressure (MAP), blood loss and need for transfusion and urine output (UOP) of patients undergoing open abdominal myomectomy.
Patient & methods: Eighty-eight patients were randomly divided into: Study patients received 200 mg oral labetalol 2-hr before surgery and IO labetalol infusion (0.2mg/kg/hr) till completion of myomectomy. Control patients received placebo infusion and all patients received the same anesthetic protocol.
Results: Operative blood loss and transfusion needs were significantly lower, but UOP was significantly higher in study than control patients. Oral labetalol significantly decreased preoperative HR and MAP of study patients compared to their baseline measures and to control patients. Oral labetalol significantly decreased HR and MAP elevations after induction and intubation compared to control patients. Labetolol infusion significantly decreased HR and MAP till stoppage of infusion compared to other measures and to control patients. Labetalol infusion allowed stability of HR and MAP with non-significant difference between measures till stoppage of infusion. Extubation significantly elevated HR and MAP in control patients, but non-significantly in study patients. Postoperative (PO), HR and MAP were significantly lower in study patients compared to baseline measures and to PO measures in control patients. PO hemoglobin concentration was significantly lower in all patients than preoperative concentrations, but concentration deficit was significantly lower in study than control patients.
Conclusion: The applied protocol of labetalol hypotensive anesthesia improved anesthetic and surgical outcome of myomectomy.
Keywords: Labetalol; Hypotensive anesthesia; Myomectomy
Abbreviations: IO: Intraoperative; PO: Postoperative; MAP: Mean Arterial Pressure; OAM: Open Abdominal Myomectomy; SNP: Sodium Nitroprusside

Introduction

Myomectomy is the gold standard uterine-sparing surgery for symptomatizing uterine fibroid [1], but intraoperative (IO) bleeding is still a challenge [2]. Hypotensive anesthesia allowed significant decrease of blood loss without compromising vital organ perfusion [3] and subsequently reduces transfusion requirements and minimizes allogenic transfusions risks [4]. Labetalol is a combined β- and α1 adrenoceptors antagonist [5]. Oral labetalol is readily absorbed in man [6]. Peak plasma level was achieved after 2.5-minute and 20-120 minutes after intravenous and oral administration, respectively [7], peak effect within 1-4hr after oral intake [8] and elimination half-life of 5 to 8 hours [6].

Hypothesis

Pre-anesthetic medication with oral labetalol followed by low- dose IO labetalol infusion can improve anesthetic and surgical outcome of open abdominal myomectomy (OAM).
Objectives: Evaluation of effect of the proposed hypotensive protocol on IO heart rate (HR) and mean arterial pressure (MAP), blood loss and need for transfusion and tissue perfusion judged by urine output (UOP) of patients undergoing OAM.
Design: Prospective comparative study.
Setting: University and Insurance hospitals, Tanta and Benha, Egypt.

Patient & Methods

This study was conducted since Oct 2014 till Nov 2016. Study protocol was approved by the Local Ethical Committee. Women assigned for myomectomy and signed written fully informed consent were included in the study. Exclusion criteria included presence of multiple myomas necessitating hysterectomy, gynecological malignancy, cardiac diseases or history of coagulopathy. Clinical evaluations entail collection of demographic data, complete gynecological and ultrasonographic examinations and routine laboratory investigations. Women with hemoglobin concentration of≤7gm/dl received preoperative blood transfusion to adjusted Hb. Conc. of ≥8gm/dl.
Patients fulfilling the inclusion criteria were randomly, using sealed envelops prepared by blinded anesthetic assistant, allocated into two equal study groups according to the applied anesthetic procedure; Study patients followed the hypotensive protocol and control patients received normotensive anesthesia.

Preparation of labetalol infusion

Labetalol infusion was prepared by mixing 4ml labetalol (Trandate injection, Aspen Pharmacare, South Africa, 5mg/ml) in 500cc physiological saline to provide a concentration of 0.04mg/ ml saline. Infusion rate was adjusted at 6ml/min, to provide the patient by 0.24mg/min, i.e., 14.4mg/hr and if the patient weighs 70kg body weight so the dose received will be 0.206mg/kg/hr [9]. Labetalol infusion rate was adjusted to provide a target MAP of 55- 60mmHg [10] but not exceeding the recommended safe maximal dose of 300mg on occasion of infusion [11]. Plain saline infusion was prepared as placebo for control patients. An assistant, not included in the study, was responsible for infusion preparations and distribution between patients and adjustment of rates.

Hypotensive protocol

Baseline HR and MAP were non-invasively determined, then study patients received 200mg oral labetalol (Trandate, Aspen Pharmacare, South Africa, 100mg tablets), while control patients received a placebo tablet two hours prior to surgery. HR and MAP were determined preoperatively, after induction of anesthesia and after tracheal intubation. Then, labetalol and placebo infusions were started till myomectomy was completed and then were stopped to allow restoration of blood pressure to achieve perfect hemostasis.

Anesthetic Procedure

Patients of control group were premedicated by midazolam 0.02mg/kg. Anesthesia was induced, in groups, using propofol 2mg/kg, fentanyl 1-2ug/kg, and rocuronium 0.6mg/kg, and was continued with sevoflurane, fentanyl and rocuronium. After tracheal intubation, the lungs were ventilated with 100% O2 in air using a semi-closed circle system for a tidal volume of 6-8 ml/ kg, and end-tidal carbon dioxide (paCO2) of 32-35mmHg. Patients were continuously non-invasively monitored for MAP and HR.

Study outcome

Primary outcome included

1. Effect of oral labetalol pre-medication on HR and MAP determined after induction and tracheal intubation.
2. Effect of labetalol infusion on intraoperative HR and MAP estimated every 10 minutes till end of surgery and at time of infusion stoppage.

Secondary outcome included

1. IO blood loss, frequency of blood transfusion
2. Amount of intraoperative UOP.
3. Hemoglobin concentration (Hb. Conc.) estimated immediately after surgery and concentration deficit in relation to preoperative concentration.

Statistical Analysis

Sample size was calculated using the standard nomogram proposed by Kraemer & Thiemann [12] and a sample size of ≥40 patients per group was determined to be sufficient to detect a difference at the 5% significance level and give the trial 80% power. Results were analyzed using paired t test, one-way ANOVA with post-hoc Tukey HSD Test and Chi-square test (X2 test). Statistical analysis was conducted using the SPSS (Version 15, 2006) for Windows statistical package. P value<0.05 was considered significant.

Results

Data are presented as mean±SD, numbers, percentages; P value indicates difference between both groups; NS: Non-significant, p<0.05: significant difference
The study included 92 patients, 26 patients (28.3%) required preoperative blood transfusion for correction of anemia and 4 patients were excluded during surgery. Mean operative blood loss and need for transfusion were significantly lower, but intraoperative UOP was significantly higher in patients of study group. Pre- and intraoperative data are shown in Table 1. Oral labetalol significantly decreased preoperative HR and MAP of patients of study group compared to their baseline measures and to preoperative measures of control patients. Induction of anesthesia and tracheal intubation significantly increased HR and MAP compared to baseline and preoperative measures in both groups. However, oral labetalol significantly decreased these elevations compared estimates of control patients.
IO labetolol infusion significantly decreased HR and MAP till stoppage of infusion in comparison to other measures and to measures of patients of control group. Moreover, labetalol infusion allowed stability of HR and MAP with non-significant difference between measures at 10-, 20-, 30-, 40-min after start of infusion and at time of stoppage of infusion. Extubation significantly elevated HR and MAP in comparison to other IO measurements in control group, while the difference was non-significant in patients of study group. At 1-hr and 2-hr postoperative (PO), mean HR and MAP levels showed non-significant difference versus baseline and preoperative measures in control group, while were significantly lower compared to baseline measures in patients of study group and to PO measures in patients of control group (Table 2). Postoperative Hb. Conc. was significantly lower in patients of both groups compared to preoperative concentration, but was non-significantly lower in patients of control group than study group. On contrary, concentration deficit was significantly lower in patients of study group compared to control group (Table 3).
*: Significant difference versus control group; f: Significant difference versus baseline measures; f: significant difference versus preoperative measures; fl: Significant difference versus after induction estimates; #: Significant difference versus after tracheal intubation estimates; $: Significant difference versus after extubation estimates.
P value indicates difference between both groups; P1 value indicates difference between preoperative and PO measures; NS: Nonsignificant, p<0.05: significant difference.

Discussion

Oral labetalol pre-medication significantly lowered preoperative HR and MAP in study patients and allowed blunting of the pressor reflexes associated with induction of anesthesia and tracheal intubation than in control patients. These findings spot light on the possibility for using oral labetalol as a preanesthetic medication and go in hand with Ryu et al. [13] who found labetalol injection either before or after laryngoscopy and tracheal intubation was associated with lower incidence of tachycardia and less increase in rate-pressure product. Also, Meftahuzzaman et al. [14] detected significantly minimal increase in HR and MAP in patients received bolus dose of labetalol or fentanyl prior to tracheal intubation compared to control patients with significant difference in favor of labetalol and concluded that labetalol is better agent for attenuation of laryngoscopic and intubation reflex than fentanyl.
Recently, El-Shmaa & El-Baradey [15] reported significant decrease in HR and MAP with labetalol and dexmedetomidine than with saline in response to laryngoscopy and intubation and Sharma et al. [16] found both labetalol and nifedipine were effective for control of persistent postpartum hypertension, but labetalol achieved control significantly more often with the starting dose and had fewer side effects. In support of the use of oral β-blockers for preoperative preparation whenever deliberate hypotension is required, Apipan & Rummasak [17], Amr & Amin [18,19] and Kim et al. [20] reported that premedication with oral propranolol, oral atenolol or oral enalapril before hypotensive anesthesia effectively reduced heart rate, amount of blood loss, and blood transfused with better quality of surgical field.
Labetalol infusion allowed proper hemodynamic control throughout operative time manifested as significantly lower MAP with subsequent significant reduction of operative field bleeding, transfusion requirement and significantly lower hemoglobin deficit compared control patients. These results coincided with previous work documented that hypotensive anesthesia reduced IO blood loss and improved the quality of the surgical field [21-]. In line with the use of labetalol infusion for maintenance of low IO blood pressure, Hadavi et al. [24] detected a little difference between labetalol and nitroglycerine on IO blood loss and surgical field quality in rhinoplasty surgery and Jeong et al. [25] found sevoflurane plus a "supportive" agent either; esmolol, labetalol, metoprolol, nicardipine, and dexmedetomidine may offer significant advantage of reducing patients' MAP than sevoflurane alone during orthognathic surgery.
The reported non-significant differences between IO measurements of MAP throughout operative time assured the proper control of labetalol infusion on blood pressure during surgical manipulation. In support of this finding, Chung et al. [26] demonstrated that labetalol pretreatment (1.2mg/kg) with supplemental intravenous sodium nitroprusside (SNP) provides more favorable blood pressure control during surgical resection of pheochromocytoma than with SNP alone.
Moreover, immediate and 2-hr PO MAP measures in study patients were significantly lower compared to baseline measures and to PO pressure in control patients. These data indicated that labetalol allowed proper emergence from anesthesia that was maintained postoperatively. These findings go in hand with Ryu et al. [13] who found time to return to normotension after the loading dose was longer with labetalol than nicardipine & Mashour et al. [27] also found the use of IO esmolol or labetalol is not associated with stroke after non-cardiac surgery, while metoprolol was associated with a 3.3-fold increase in perioperative stroke. Moreover, Sanath Kumar et al. [28] presented four cases of phaeochromocytoma prepared with oral labetalol and reported rare intraoperative surges in blood pressure during tumor manipulation and all patients had an uneventful PO recovery. Sirivanasandha et al. [29] documented that labetalol is a good alternative drug to control hypertensive response during emergence from anesthesia for post-craniotomy.

Conclusion

The applied protocol of oral labetalol pre-medication and low- dose IO labetalol infusion as a modality for hypotensive anesthesia improved anesthetic and surgical outcome of myomectomy.
For more Open Access Journals in Juniper Publishers please click on: https://juniperpublishers.com
For more articles in Journal of Anesthesia & Intensive Care Medicine please click on: https://juniperpublishers.com/jaicm/index.php
For more Open Access Journals please click on: https://juniperpublishers.com

33F , 5’6” 270 Lbs Caucasian Greater Boston Area
Current Medications: Labetalol 300 mg TID Weekly Vitamin D 10000 IU Daily anti histimine
Lifestyle: No drinking for the last 9 months (pregnancy) prior to pregnancy 1-2 drinks /week
No recreational drugs or tobacco use (ever)
Other diagnoses: Chronic Hypertension (over 10 years) - I Internalize my stress which contributes to / causes this
Currently have a 18k White blood cell count. It’s been elevated for years and my GP is unconcerned but I am (perhaps this is a case of why patients shouldn’t get raw lab results). I was referred to hematology specialist who insisted it was due to my weight. I went on a diet and lost ~80 pounds and the WBC didn’t change. So he was stumped and didn’t take it any further. Before asking my PCP for another referral (perhaps in Boston or the Medical school in Worcester) I thought I’d ask here.
Potentially unrelated - I sweat. A lot. Even when it’s not hot or I haven’t been entering myself. This could totally be related to my weight and I only mention it as it’s odd.
Thank you in advance

41 yr old female, 170 lbs, white, New Hampshire, USA (regular medications: Albuterol for Asthma, Soolantra for rosacea and Labetalol for high blood pressure. Also taking 500 mg of Amoxicillin 4x per day post tooth extraction ).
I had a tooth extraction and bone graft done today. As a nervous patient with health anxiety my primary doctor prescribed me alprazolam to take for the procedure. I took two .25 mg pills (.5 mg total) pills at 1:30pm today. The oral surgeon's office was aware of this. I was awake for the procedure - I had local anesthetic and nitrous gas. They prescribed me 6 pills of Norco (5/325 hydrocodone/acetaminophen) in case I needed them for pain. It is 9:00pm now and I have not needed to take the Norco yet (been icing and they gave me 600 mg of ibuprofen before I left their office at 4:30pm) but I was reading the pamphlet and see that Norco can have a dangerous and sometimes fatal interaction with Alprazolam.
I do not plan on taking any more alprazolam and if I do need to take the Norco it will probably be 10 or 12 hours since I took the alprazolam. Is there a certain number of hours apart where it is safe to have taken these two drugs? I'm hoping I don't need to take the Norco anyhow, but if I do need it, is it safe to take it 10 or 12 hours apart from the Alprazolam? Both the surgeon's office and my pharmacy is closed at this hour so that is why I was asking here.

History....

• Was morbidly obese most of my adult life - hovering around 80-100 pounds overweight.
• Over the past 5 years I slowly lost 80 pounds which got me down to 190 at 5'10" (86 kg at 178 cm)
• I gained a bit of weight back before I got pregnant which put me back at around 205 pounds
• Have a history of high blood pressure but I take 200 mg labetalol 100 mg 2x/day and it's perfect at 120/80.
• Used to run (slowly) and ride my bike everywhere.
• I am from the states, but have been living in Argentina for the past 8 years.

Currently

• Just turned 42
• I am at 22 weeks and have gained 20 pounds so far. Both my OB and my regular Dr want me to not gain any more weight. So that means eating at a deficit while I put on baby weight so that I lose fat.
• Now I am swimming 3x/week and walking and some prenatal yoga (but honestly not much)

Has anyone else done this? Has anyone else done this successfully? I have done a bunch of research online and there are various reports. I am wondering about my health and about fetal health and trying to optimize for both and am very confused.