\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Cardiovascular Collapse during Laparoscopy: A Brief Overview}



\author[1]{Brian Wildey}%
\author[1]{Mostafa Borahay}%
\author[1]{David Berman}%
\affil[1]{Johns Hopkins Medicine School of Medicine}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
This review article considers the physiology, differential diagnosis and
immediate management of vasovagal response, vascular injury and carbon
dioxide embolism caused during creation of the laparoscopic
pneumoperitonium. These pathologies account for over half of all
laparoscopic complications and therefore, by taking a systematic
approach to these possibly life-threatening events, laparoscopy can
become even safer.%
\end{abstract}%



\sloppy


\textbf{Introduction}

The introduction of laparoscopy has revolutionized modern surgery. As
more procedures are performed with laparoscopic techniques, the use of
laparotomy and other open techniques have declined. Patients undergoing
these minimally invasive procedures are having shorter lengths of
hospital stay, less pain, quicker recovery and, in many instances, the
overall cost of the procedure is less\textsuperscript{1-3}. However, the
introduction of laparoscopy has brought unique complications. This
review article will discuss the rare yet possibly fatal risk of
cardiovascular collapse during laparoscopy.

The first laparoscope was performed in the early
20\textsuperscript{th}century. Quickly pneumoperitoneum protocols were
established to improve intraabdominal visualization. By 1968, the Verres
needle was invented and carbon dioxide was used routinely as an
insufflation gas. Carbon dioxide has become a mainstay of laparoscopy
because it is inexpensive, readily available, non-flammable, colorless
and highly soluble in blood. Early laparoscopic techniques were
developed in the gynecological realm specifically to cause permanent
sterilization. Early laparoscopic gynecologists would insert the Verres
needle into the posterior cul-de-sac or even into the cervix and through
the uterine fundus to begin insufflation\textsuperscript{4,5}. These
techniques encountered some complications and therefore placing the
insufflating device through the abdominal wall has become more
commonplace.

The combination of blind entry into the abdomen and the exposure of the
patient to carbon dioxide gas has created some unique opportunities for
cardiovascular collapse to occur during laparoscopic procedures.
Estimates of laparoscopic mortality range from 1-4/100,000
cases\textsuperscript{3,5,6}with 50\% of all major laparoscopic
complications occurring at abdominal entry and
insufflation\textsuperscript{1}. There is a 1/2,500 incidence of cardiac
arrest during laparoscopy\textsuperscript{6} with a 14\% rate of
dysrhythmias\textsuperscript{3}. This review article will briefly review
the normal physiological alterations caused by a carbon dioxide
pneumoperitoneum and then discuss the leading causes of cardiovascular
collapse related to the formation of that pneumoperitoneum. We will then
touch upon the differential diagnosis of these causes and immediate
management of the patient experiencing cardiovascular collapse.

\textbf{Physiology}

Carbon dioxide is found in the blood of all living humans as it is a
major by-product of metabolism. With a normally functioning
cardiopulmonary system, that carbon dioxide is carried out of the body
and eliminated by lung exhalation. If this carbon dioxide is not
eliminated, it can cause respiratory acidemia with a myriad of
complications to the patient including cardia arrhythmias. The creation
of a pneumoperitoneum increases the amount of carbon dioxide in the
body. Carbon dioxide can be absorbed when coming into contact with the
peritoneum or can be inadvertently introduced into an injured blood
vessel. Carbon dioxide gas can also unintentionally be introduced into
the subcutaneous tissue causing subcutaneous emphysema. It is thought
this occurs in up to 2\% of laparoscopies leaving another reservoir of
carbon dioxide that must be ventilated off\textsuperscript{7}. One study
found that peak serum carbon dioxide levels occur 10 minutes after
insufflation\textsuperscript{3,8}and persist for 45 minutes after the
pneumoperitoneum is released\textsuperscript{3}. Most patients,
especially when ventilated, can easily clear this excess carbon dioxide.
Anesthesiologists often adjust minute ventilation to account for this
increase in carbon dioxide uptake, allowing a normal acid-base status to
be maintained during surgery.

The act of creating the pneumoperitoneum does create some boundaries to
clearing that carbon dioxide. The pneumoperitoneum places upwards
pressure on the abdominal wall to increase visualization but also
increases pressure on the diaphragm and inferior vena cava. Pressure on
the diaphragm decreases lung volume and therefore gas exchange making it
harder for carbon dioxide to be eliminated. Trendelenburg position is
frequently used in laparoscopy and it also causes pressure on the
diaphragm by shifting the abdominal consents against the diaphragm. All
of these changes serve to worsen lung compliance, lowering tidal volumes
and increasing the risk of barotrauma with mechanical ventilation. While
well-tolerated in young and healthy patients, this ventilator impairment
can pose a challenge for older or morbidly-obese patients. Pressure on
the inferior vena cava will also decrease blood return to the heart and
hence cardiac output. Therefore, less carbon dioxide makes it to the
lungs to be eliminated and heart perfusion is decreased. Decrease in
myocardial oxygen delivery also leads to arrhythmia. One study found
that when the pneumoperitoneum exceeds 15 mmHg cardiac output can be
decreased by 28\%\textsuperscript{4}. Again, these physiological changes
can be compensated for in a healthy ventilated patient. Obese patients
and patients with pre-existing heart and lung disease will need closer
monitoring to compensate for their pathophysiology\textsuperscript{7}.
The speed at which the pneumoperitoneum is created also has effects on
the sympathetic nervous system. The rapid stretching of the peritoneum
with insufflation greatly increases vagal tone\textsuperscript{8}. This
rush of sympathetic response leads to hypotension and bradycardia even
to the point of asystole.

\textbf{Leading causes}

The above-mentioned vagal response is a cause of cardiovascular collapse
during laparoscopy. This pathophysiology is usually self-limiting in a
healthy patient. By releasing the pneumoperitoneum and supporting the
patient while the sympathetic nervous system resets, normal
cardiopulmonary physiology can usually be reestablished. Additionally,
antimuscarinic agents (either glycopyrrolate or atropine) are often
administered by the anesthesia team to combat bradycardia, interrupting
the vagal signaling arc and decreasing the incidence of bradycardia.
Glycopyrrolate has a longer duration of action and does not cause
central anticholinergic syndrome, but is the slower-onset of the two
commonly-used antimuscarinics. Occasionally, sympathomimetics (ephedrine
or epinephrine) are needed to raise the heart rate if unresponsive to
atropine. The other two leading causes of cardiovascular collapse can be
much more malignant and require more intervention. These are accidental
vascular injury and/or carbon dioxide embolism caused in relation to the
formation of the pneumoperitoneum.

The rate of vascular injury is 0.03\%-0.06\%\textsuperscript{3}. An
Australian study reported a rate of 7/10,000 for vascular injury with a
23-56\% mortality rate resulting\textsuperscript{9}. The most common
injured major blood vessels are the abdominal aorta followed by the
common iliac vessels however mesenteric and all other intraabdominal
vessels are at risk. The injury of these large vessels leads to
exsanguination and resulting hemorrhagic sock. This condition is
diagnosed first by a flash of blood through the insufflating device
followed by tachycardia and hypotension. These are the hallmarks of
acute blood loss. Cardiovascular collapse ensues when intravascular
volume and pressure are lost and the heart, as well as other organs, are
no longer perfused.

The incidence of carbon dioxide embolism during laparoscopy is much more
elusive. Trans-esophageal echocardiogram during routine laparoscopy has
shown gas bubbles present in the right heart in 6.25 to 100\% of all
cases\textsuperscript{10,11}. Granted, the majority of these emboli are
asymptomatic. It is estimated that clinically relevant emboli occur in
0.001\% of laparoscopies of which 28\% are fatal\textsuperscript{10}.
Dog and pig studies have demonstrated that it would take greater than 70
cc/minute of direct injection of intravascular carbon dioxide to cause
cardiovascular collapse\textsuperscript{4,11}. Normal laparoscopic low
flow rates should only introduce 5\% of that volume\textsuperscript{10}.
Carbon dioxide embolism causes gas bubbles to be trapped and occlude the
pulmonary vasculature. This results in a V-Q mismatch which causes
hypoxia and hypercapnia. This loss of oxygen and respiratory acidemia
results in decreased oxygenation and acidosis of the heart and other
organs and organ failure. Carbon dioxide embolism is diagnosed by
cyanosis, bradycardia and hypotension. End tidal carbon dioxide,
measured during ventilation, rapidly increases then drops off
dramatically. The pathognomonic mill-wheel murmur is heard as trapped
gas bubbles are heard in the right heart. Precordial Doppler has been
used in the past to also recognize this trapped gas. While rare, carbon
dioxide may also cross a patent foramen ovale and cause arterial
occlusion. This is considerably less dangerous than arterial air given
the solubility of carbon dioxide in blood, but nonetheless is a
potential cause of embolic stroke.

\textbf{Immediate management}

The key to managing this possibly life-threatening complications lies in
making the correct diagnosis. Vascular injury, after identified, should
start with leaving the insufflation device in place. The Veress needle,
or other insufflating device, can serve to occlude the damaged vessel
and removing the instrument may allow blood to rapidly leave the
vasculature and even make the rent in the vessel larger. An exploratory
laparotomy can then be performed where the damaged vessel is identified,
the insufflation instrument removed under direct visualization and the
vessel repaired. It would be advantageous at this point to recruit the
assistance of vascular surgery or other specialists well practiced in
large vessel repair. This event should be immediately communicated to
the anesthesia team who can begin volume resuscitation, replacement of
blood products and even possible pressor support to maintain perfusion
and avoid further hemorrhagic shock. Consideration should also be made
for aortic cross-clamping or using an aortic occlusion balloon, both of
which are routinely used in aortic surgery by vascular surgeons for
hemorrhage control. Care should be taken to place the clamp as distal as
possible, to avoid renal and gastrointestinal tract ischemia, and to
avoid clamping the inferior vena cava.

The management of carbon dioxide embolism is significantly different and
therefore the need to make the correct diagnosis. The mainstay of carbon
dioxide embolism treatment is to stop insufflating gas into the patient.
The gas should be turned off and the pneumoperitoneum released. All of
these actions will decrease more carbon dioxide from entering the blood
stream. Again, this should be communicated to the anesthesia team who
can also help with the diagnosis (end tidal carbon dioxide readings and
mill-wheel murmur). The anesthesiologist can then hyperventilate the
patient to remove the carbon dioxide and position the patient on their
left side to trap carbon dioxide bubbles in the upper right atrium and
away from the pulmonary vasculature. In extreme cases, a central venous
line can be placed and gas bubbles removed from the right heart, though
typically by the time the line is placed the carbon dioxide has already
been absorbed: this is most helpful in patients with indwelling central
venous catheters. Hyperbaric therapy has been used to treat cerebral gas
emboli which arrived in the brain by a patent foramen ovale (paradoxical
emboli), an uncommon sequela of this uncommon condition.

\textbf{Future Questions}

This review article has covered why the pneumoperitoneum, unique to
laparoscopy, can cause life threatening complications. Pneumoperitoneum
physiology, common reasons for cardiovascular collapse on insufflation
and their respective management have been covered. However, there are a
few questions that remain to be addressed in relation to this topic. 1)
If a vagal response or small carbon dioxide embolism is successfully
managed if and when should re-insufflation be attempted. How much slower
a rate of insufflation and pressure should be used? 2) What is the
safest entry into the abdominal cavity to allow insufflation. A Cochrane
review has tried to address this issue and even a recent update to that
review has still shown inconclusive results\textsuperscript{12}.

\textbf{Medicolegal and Ethical Considerations}

These further research questions also bring up some ethical and legal
areas of interest. The above mentioned pathologies are rare and
frequently self-limited. Quality care is transparent care and therefore
these possibly fatal complications should be presented to our patients
during the consent process. We should also be clear to our patients that
there are limited ways to mitigate these risks and that entry techniques
vary greatly between surgeons\textsuperscript{13}. If these events
occur, they should be communicated to the patient in the post-operative
area. These events, and their management, should also be documented in
the operative report. This communication will be invaluable for the next
laparoscopist and anesthesiologist.

Sandberg et al found that more than a third of Dutch laparoscopic
malpractice claims were entry related. The number of claims has stayed
relatively constant over the last twenty years\textsuperscript{14}.
However, the United Kingdom case of Palmer v Cardiff and Vale NHS has
established precedent, at least in England, that injury during
laparoscopic entry is considered negligent\textsuperscript{13}. If
litigation were to be pursued, then a clear and thorough documentation
of events and the thought process behind management will assist in
making intent very clear to other parties.

Intraoperative decisions frequently need to be made without the
assistance of our patients. If a vagal response or carbon dioxide emboli
is managed successfully, the decision to reattempt insufflation is made
solely by the patient's surgeon and anesthesiologist. Shared decision
making becomes near impossible when one half of the parties involved are
under general anesthesia. There appears to be no way around this but it
is a humbling thought none-the-less and again speaks to a thorough
consent process.

Finally, should laparoscopy be performed in a setting where an
anesthesiologist and/or surgeon trained in large vessel repair are not
readily available? Safety is paramount but limiting access to the
benefits of minimally invasive procedures seems to be an undue burden
for such rare events. The benefits of minimally invasive laparoscopic
procedures are great and with further research and this review article
hopefully the risks can be further mitigated.

\textbf{Conflict of Interest Statement}

The authors have no conflict of interest to declare

\textbf{Author Contribution Statement}

BW, DB and MAB all contributed to this review conception and design,
interpreting the relevant literature and manuscript preparation and
revision. BW, DB and MAB all have reviewed and approve the final
manuscript.

References

1. Gershenson DMLGMVFALRA. Comprehensive gynecology. 2022;
https://www.vlebooks.com/vleweb/product/openreader?id=none\&isbn=9780323790789.

2. Jones HW. \emph{Te Lindes Operative Gynecology.} Lippincott, Williams
\& Wilkins; 2015.

3. Joshi GP. Complications of laparoscopy. \emph{Anesthesiology clinics
of North America.}2001;19(1):89-105.

4. Morison DH, Riggs JR. Cardiovascular collapse in laparoscopy.
\emph{Canadian Medical Association journal.} 1974;111(5):433-437.

5. Ostman PL, Pantle-Fisher FH, Faure EA, Glosten B. Circulatory
collapse during laparoscopy. \emph{Journal of clinical anesthesia.}
1990;2(2):129-132.

6. Biswas TK, Pembroke A. Asystolic cardiac arrest during laparoscopic
cholecystectomy. \emph{Anaesthesia and intensive care.}
1994;22(3):289-291.

7. Atkinson TM, Giraud GD, Togioka BM, Jones DB, Cigarroa JE.
Cardiovascular and Ventilatory Consequences of Laparoscopic Surgery.
\emph{Circulation.} 2017;135(7):700-710.

8. Takrouri MS. Anesthesia for laparoscopic general surgery. A special
review. \emph{Middle East journal of anaesthesiology.} 1999;15(1):39-62.

9. Hanney RM, Alle KM, Cregan PC. Major vascular injury and laparoscopy.
\emph{The Australian and New Zealand journal of surgery.}
1995;65(7):533-535.

10. Park EY, Kwon JY, Kim KJ. Carbon dioxide embolism during
laparoscopic surgery. \emph{Yonsei medical journal.} 2012;53(3):459-466.

11. Orhurhu VJ, Gao CC, Ku C. Carbon Dioxide Embolism. \emph{StatPearls}
. Treasure Island (FL)2021.

12. Ahmad G, Baker J, Finnerty J, Phillips K, Watson A. Laparoscopic
entry techniques. \emph{Cochrane Database of Systematic Reviews.}
2019(1).

13. Varma R, Gupta JK. Laparoscopic entry techniques: clinical
guideline, national survey, and medicolegal ramifications.
\emph{Surgical endoscopy.} 2008;22(12):2686-2697.

14. Sandberg EM, Bordewijk EM, Klemann D, Driessen SRC, Twijnstra ARH,
Jansen FW. Medical malpractice claims in laparoscopic gynecologic
surgery: a Dutch overview of 20 years. \emph{Surgical endoscopy.}
2017;31(12):5418-5426.

\textbf{Hosted file}

\verb`figure1.docx`  available at \url{https://authorea.com/users/494816/articles/576765-cardiovascular-collapse-during-laparoscopy-a-brief-overview}

\selectlanguage{english}
\FloatBarrier
\end{document}

